clinical relationship of fcov/fipv infectionsvet.kku.ac.th/yaopdf/pptkvac2015/data/24103.pdfclinical...
TRANSCRIPT
Clinical relationship of FCoVFIPV infections
Assoc Professor Parnchitt Nilkumhang KVAC 2015 One Health Workforces Best Practices in Thailand
Venue Centara and Convention Center Hotel Khonkaen July 24th 2015
FIP is difficult to diagnose and treated
FIP diagnosis and treatment are frustrated to well communication
Diagnosis of FIP A frustation
bull Clinical Examination and environmental consideration
bull Laboratory supports
bull Imaging findings
bull Cytology Serology and molecular diagnosis
bull Histopathological confirmation
What is the PROBLEM of FIP diagnosis
bull Sick cats presented with no effusion (pleural peritoneal cavity)
ldquo dry FIP ldquo
bull Normalhealthy shedder cats
Physical and Environmental findings
Multifactoral risk
bull Owner bull Multi-cat household
bull Cat bull Age blood line
bull Pure breeds gt DSH
bull Immune response
bull Virus bull Mutation
bull Uncertain period (exposed to clinically sick)
bull Environment bull Stress
bull Physical findings Depend on when the
cats are presented
ndash Early
ndash Mid
ndash Late
How does ldquoAGErdquo of sick cat help the diagnosis
Inc period 2-14 days (exprsquol) bull FCoV in feces found as
early as 2 days after exposure (main site is colon)
bull Clinical FIP found as early as 2 wk old to 18 months
and elderly gt 12 yr
bull From pyogranulomatous inflammation to clinical signs may be many months
How does ldquoAGErdquo of sick cat help the diagnosis
bull Pattern of virus nature
bull Pathogenesis of virulentnon virulent virus
bull Exposure time to clinical
sickness
bull Factors of immune response
bull Concurrent diseases
Inc period 2-14 days (exprsquol) bull FCoV in feces found as
early as 2 days after exposure (main site is colon)
bull Clinical FIP found as early as 2 wk old to 18 months
and elderly gt 12 yr
bull From pyogranulomatous inflammation to clinical signs may be many months
เรามาถงจดนไดอยางไร
Objective Knowing FCoVs
Clinical relationship of FCoVs FECV and FIPV
Feline coronavirus classification flowchart
A Kipar and M L Meli Vet Pathol 201451505-526
Copyright copy by American College of Veterinary Pathologists
Feline coronavirus classification flowchart
A Kipar and M L Meli Vet Pathol 201451505-526
Copyright copy by American College of Veterinary Pathologists
CCoV FCoV TGEV
bull All group 1 Coronavirus are antigenically related
bull FCoV is divided into 2 serotypes bull FCoV 1
bull FCoV 2
bull FCoV 2 is antigenically similar to CCoV
( FCoV 2 is a recombinant of FCoV and CCoV)
bull BUT most field-strains are FCoV 1
Genetic relationships between the different feline and canine
coronaviruses genotypes (FCoV CCoV and TGEV)
From wwwgooglecom
FCoVs ndashwho are they
FCoV I
FCoV II
2 serotypes
FCoVs ndashwho are they
FCoV I
FCoV II
2 serotypes
2 biotypes pathotypes
FECV
FIPV
Enteric biotype Virulent biotype
FECVFIPV -serologicalmorphological undistinguishable
Prevalence of Feline Coronaviruses (FCoV)
Housed cats
bull 25-40 of cats infected with FCoV
Multi cat household colonies
bull 80-100 of cats infected with FCoV
In high prevalent area occurrence of FIP ~ 10
How FECV turn into FIPV
bull Two theories
ndash Internal mutation
ndash Circulating virulent avirulent viruses
bull FIPV and FECV strains can be serotpye I or II
Mutation when FECV turns into FIPV
Internal mutation theory
bull Genetic changes from FECV to FIPV in individual infected cat
bull Various types of mutation within 3c gene
bull 20 of kittens infected with FECV will produce an FIP mutant
Molecular Studies for diagnosis of FIP
bull Conflicting results
bull FCoV 1 (FIPV I) hellipvirulent bull FCoV II (FIPV II)hellipnon-virulent
Pathogenesis of FIP controversial
bull Immune-mediated vasculitis
bull Immune complex Type 3 hypersensitivity disease
Ag + Ab +compliments +C3
bull Pathological morphology
ndash Activation of monocytes
macrophages
ndash Monocyte-mediated viremia
ndash Granulomatous phleblitis periphlebitis
ndash VEGF ndash mediators increase vascular permeability
Endothelial cells show strongly MHCII antigen positive
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Activated macrophages
Morphologic Features and Development of Granulomatous vasculitis in FIP Kipar et al(2005)
Emigration of FCoV ndashinfected monocytes to vascular perivascular granulomatous infiltrates
with destruction of vascular basal laminar
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Leptomeningeal veins Agglomerate of TNF-α-positive monocytes attached to
venous endothelium Avidin-biotin-peroxidase complex method Papanicolaous hematoxylin counterstain Bar = 10 μm
Objective bullKnowing FCoVs
bullFCoVs in clinical diagnosis
Serology and Molecular diagnosis
Indirect FCoV antibody test Direct (viral load) FCoV RT-PCR
bull Blood
bull Feces
bull Effusion fluid
bull CSF
bull At present NO nucleoprotein sequences unique to pathogenic FCoV (ie not also present in nonpathogenic FCoV) have been identified
FCoV FECV FCoV where are they
Small intestinal enterocytes
Colon -rectum
Healthy shedders
Asymptomatic or mild diarrhea
After clearance from sm intestine FCoVs spread to infect colon and intermittently shedded off
If kittens infected before immune system fully mature levels of FECV replication will be very high
Reinfection may be from FCoV same strains or different strains
Pyogranulomatous inflammation
FIPV infected monocytes perivascular macrophages overproduce neutrophil survival factors Tumor necrosis factor- alpha (TNF ndashalpha) bull Matrix metalloproyeinase-9 bull GM-CSF bull G-CSF Neutrophil survival Development of granuloma lesions
Interpretation of FCoV antibody test
Viral shedding ~ 2 days (FCoV in epithelial cells)
Signs of FIP
bull As early as 2 wk old to 18 months
bull From pyogranulomatous inflammation to clinical signs may be months
From NC Pederson et al (2008) Feline enteric coronavirus infection
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To rule out FIP in sick cats bull effusive FIP
bull non- effusive FIP ( esp cats with GI signs)
bull To screen the FCoV excretors bull Cats in contact with known FCoV shedder
bull Cats in the household
bull New kitten or new cat bringing into the multi-cat household
bull Before receiving immunosuppressive treatment or stressful procedures
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To screen a breeding queen
bull To monitor FIP treatment q 8-12 wks
bull To screen blood donor cat
bull To screen prior to FeLV vaccination
Blood fluid Interpretation of FCoV antibody test
I false negative in sick FIP cat
II High titer (gt 11600) in normal cat (esp cat from multi-household) is not indicated FIP
III High titer in fluid high PPV
IV Generally not recommended in sick cat
FCoV antibody in CSF
bull Use of anti-coronavirus antibody testing of cerebrospinal fluid for diagnosis of feline infectious peritonitis involving the central nervous system in cats
bull J Am Vet Med Assoc January 2007230(2)199-205
bull Irene C Boettcher1 Tanja Steinberg Kaspar Matiasek Craig E Greene Katrin Hartmann Andrea Fischer
CSF IgG was detected only in strongly seropositive cats suggested that CSF anti-coronavirus IgG was derived from blood Measurement of
anti-coronavirus IgG in CSF was of equivocal clinical use
Test test test
FCoV RT-PCR test ( bloodeffusion fluidfeces)
Blood FCoV RT-PCR FECV Monocyte-associated viremia Not differentiate FIPV from pathotype
FCoV
Fecal FCoV RT-PC Recommend for house-cat management BUT single positive or negative tests are
meaningless as cats may shed intermittently or may be recently infected
Effusion fluid FCoV RT-PCR bull Generally recommended for fluid bull Positive result high PPV bull But 30 of effusions from cats
with FIP may be negative by RT-PCR
Why false negative 1 FIPV is cell-associated and likely confined to cells of perivascular granuloma (leaking out of pure plasma) 2 Inhibition of RT-PCR by interfering substances in fluid Therefore negative result doesnrsquot exclude FIP
Is FIP a contagious disease (cat-to-cat transmission)
Is FIP a contagious disease (cat-to-cat transmission)
Cats with FIP do not excrete pathogenic FIPV
FECV in enterocytes
Is FIP contagious
Cats with FIP do not appear to be very contagious to cats coming in contact with
Every FIPV isolated from a group outbreak of FIP does NOT genetically identical in its 3c gene mutation
However FIPV is found in the feces of most cats with FIP
Mutation when FECV turns into FIPV
Internal mutation theory bull Genetic changes from FECV
to FIPV
bull Various types of mutation within OPFs 3 and 7
bull 20 of kittens infected with FECV will produce an FIP mutant
Horizontal (cat-to cat) bull Transmission of FIPV
mutants
bull cats with FIP are shedding the same FIPV in their feces
J Gen Virol 2010 Feb91(Pt 2)415-20 doi 101099vir0016485-0 Epub 2009 Nov 4
Feline infectious peritonitis insights into feline coronavirus
pathobiogenesis and epidemiology based on genetic analysis of the viral
3c gene Chang HW1 de Groot RJ Egberink HF Rottier PJ
helliphellipMost cats with FIP had no detectable intestinal feline coronaviruses (FCoVs) and
had seemingly cleared the primary FECV infection In those with detectable intestinal
FCoV the virus always had an intact 3c and seemed to have been acquired by FECV
superinfection Apparently 3c-inactivated viruses replicate not at all--or only poorly--in the
gut explaining the rare incidence of FIP outbreaks
FIP transmission
FIP transmission
bull Vet Res 2013 Jul 174457 doi 1011861297-9716-44-57
bull An outbreak of feline infectious peritonitis in a Taiwanese shelter epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus
bull Wang YT1 Su BL Hsieh LE Chueh LL
bull Abstract
bull helliphellipSequence analysis revealed that the type II FIPV detected from fecal samples body
effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death Taken together our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment
FCoV field strain in FIP cat
Genomic RNA sequence of feline coronavirus strain FCoV C1Je Charlotte Dye BVMampS PhD CertSAM MRCVS
Stuart G Siddell BSc(Hons) PhD
bull This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV) Viral RNAs isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP) derived 100 nucleotide identity
Feline Coronavirus serotypes I and II were reported in natural infection
bull Feline coronavirus serotypes 1 and 2 seroprevalence and association with disease in Switzerland
bull Clin Diagn Lab Immunol October 200512(10)1209-15 bull Maya Kummrow1 Marina L Meli Michael Haessig Enikoe Goenczi Amy Poland Niels C
Pedersen Regina Hofmann-Lehmann Hans Lutz
bull Comparison of serologic techniques for the detection of antibodies against feline coronaviruses
bull J Vet Diagn Invest January 200820(1)45-50 bull Annamaria Pratelli1
bull Prevalence of Korean cats with natural feline coronavirus infections bull Virol J January 20118(0)455 bull Dong-Jun An1 Hye-Young Jeoung Wooseog Jeong Jee Yong Park Myoung-Heon Lee Bong
Kyun Park bull 1National Veterinary Research and Quarantine Service Anyang Kyunggi-do430-824 Korea
bull Moreshellip
Take home message Knowing ME knowing YOU
My team my world
Thank you
FIP is difficult to diagnose and treated
FIP diagnosis and treatment are frustrated to well communication
Diagnosis of FIP A frustation
bull Clinical Examination and environmental consideration
bull Laboratory supports
bull Imaging findings
bull Cytology Serology and molecular diagnosis
bull Histopathological confirmation
What is the PROBLEM of FIP diagnosis
bull Sick cats presented with no effusion (pleural peritoneal cavity)
ldquo dry FIP ldquo
bull Normalhealthy shedder cats
Physical and Environmental findings
Multifactoral risk
bull Owner bull Multi-cat household
bull Cat bull Age blood line
bull Pure breeds gt DSH
bull Immune response
bull Virus bull Mutation
bull Uncertain period (exposed to clinically sick)
bull Environment bull Stress
bull Physical findings Depend on when the
cats are presented
ndash Early
ndash Mid
ndash Late
How does ldquoAGErdquo of sick cat help the diagnosis
Inc period 2-14 days (exprsquol) bull FCoV in feces found as
early as 2 days after exposure (main site is colon)
bull Clinical FIP found as early as 2 wk old to 18 months
and elderly gt 12 yr
bull From pyogranulomatous inflammation to clinical signs may be many months
How does ldquoAGErdquo of sick cat help the diagnosis
bull Pattern of virus nature
bull Pathogenesis of virulentnon virulent virus
bull Exposure time to clinical
sickness
bull Factors of immune response
bull Concurrent diseases
Inc period 2-14 days (exprsquol) bull FCoV in feces found as
early as 2 days after exposure (main site is colon)
bull Clinical FIP found as early as 2 wk old to 18 months
and elderly gt 12 yr
bull From pyogranulomatous inflammation to clinical signs may be many months
เรามาถงจดนไดอยางไร
Objective Knowing FCoVs
Clinical relationship of FCoVs FECV and FIPV
Feline coronavirus classification flowchart
A Kipar and M L Meli Vet Pathol 201451505-526
Copyright copy by American College of Veterinary Pathologists
Feline coronavirus classification flowchart
A Kipar and M L Meli Vet Pathol 201451505-526
Copyright copy by American College of Veterinary Pathologists
CCoV FCoV TGEV
bull All group 1 Coronavirus are antigenically related
bull FCoV is divided into 2 serotypes bull FCoV 1
bull FCoV 2
bull FCoV 2 is antigenically similar to CCoV
( FCoV 2 is a recombinant of FCoV and CCoV)
bull BUT most field-strains are FCoV 1
Genetic relationships between the different feline and canine
coronaviruses genotypes (FCoV CCoV and TGEV)
From wwwgooglecom
FCoVs ndashwho are they
FCoV I
FCoV II
2 serotypes
FCoVs ndashwho are they
FCoV I
FCoV II
2 serotypes
2 biotypes pathotypes
FECV
FIPV
Enteric biotype Virulent biotype
FECVFIPV -serologicalmorphological undistinguishable
Prevalence of Feline Coronaviruses (FCoV)
Housed cats
bull 25-40 of cats infected with FCoV
Multi cat household colonies
bull 80-100 of cats infected with FCoV
In high prevalent area occurrence of FIP ~ 10
How FECV turn into FIPV
bull Two theories
ndash Internal mutation
ndash Circulating virulent avirulent viruses
bull FIPV and FECV strains can be serotpye I or II
Mutation when FECV turns into FIPV
Internal mutation theory
bull Genetic changes from FECV to FIPV in individual infected cat
bull Various types of mutation within 3c gene
bull 20 of kittens infected with FECV will produce an FIP mutant
Molecular Studies for diagnosis of FIP
bull Conflicting results
bull FCoV 1 (FIPV I) hellipvirulent bull FCoV II (FIPV II)hellipnon-virulent
Pathogenesis of FIP controversial
bull Immune-mediated vasculitis
bull Immune complex Type 3 hypersensitivity disease
Ag + Ab +compliments +C3
bull Pathological morphology
ndash Activation of monocytes
macrophages
ndash Monocyte-mediated viremia
ndash Granulomatous phleblitis periphlebitis
ndash VEGF ndash mediators increase vascular permeability
Endothelial cells show strongly MHCII antigen positive
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Activated macrophages
Morphologic Features and Development of Granulomatous vasculitis in FIP Kipar et al(2005)
Emigration of FCoV ndashinfected monocytes to vascular perivascular granulomatous infiltrates
with destruction of vascular basal laminar
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Leptomeningeal veins Agglomerate of TNF-α-positive monocytes attached to
venous endothelium Avidin-biotin-peroxidase complex method Papanicolaous hematoxylin counterstain Bar = 10 μm
Objective bullKnowing FCoVs
bullFCoVs in clinical diagnosis
Serology and Molecular diagnosis
Indirect FCoV antibody test Direct (viral load) FCoV RT-PCR
bull Blood
bull Feces
bull Effusion fluid
bull CSF
bull At present NO nucleoprotein sequences unique to pathogenic FCoV (ie not also present in nonpathogenic FCoV) have been identified
FCoV FECV FCoV where are they
Small intestinal enterocytes
Colon -rectum
Healthy shedders
Asymptomatic or mild diarrhea
After clearance from sm intestine FCoVs spread to infect colon and intermittently shedded off
If kittens infected before immune system fully mature levels of FECV replication will be very high
Reinfection may be from FCoV same strains or different strains
Pyogranulomatous inflammation
FIPV infected monocytes perivascular macrophages overproduce neutrophil survival factors Tumor necrosis factor- alpha (TNF ndashalpha) bull Matrix metalloproyeinase-9 bull GM-CSF bull G-CSF Neutrophil survival Development of granuloma lesions
Interpretation of FCoV antibody test
Viral shedding ~ 2 days (FCoV in epithelial cells)
Signs of FIP
bull As early as 2 wk old to 18 months
bull From pyogranulomatous inflammation to clinical signs may be months
From NC Pederson et al (2008) Feline enteric coronavirus infection
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To rule out FIP in sick cats bull effusive FIP
bull non- effusive FIP ( esp cats with GI signs)
bull To screen the FCoV excretors bull Cats in contact with known FCoV shedder
bull Cats in the household
bull New kitten or new cat bringing into the multi-cat household
bull Before receiving immunosuppressive treatment or stressful procedures
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To screen a breeding queen
bull To monitor FIP treatment q 8-12 wks
bull To screen blood donor cat
bull To screen prior to FeLV vaccination
Blood fluid Interpretation of FCoV antibody test
I false negative in sick FIP cat
II High titer (gt 11600) in normal cat (esp cat from multi-household) is not indicated FIP
III High titer in fluid high PPV
IV Generally not recommended in sick cat
FCoV antibody in CSF
bull Use of anti-coronavirus antibody testing of cerebrospinal fluid for diagnosis of feline infectious peritonitis involving the central nervous system in cats
bull J Am Vet Med Assoc January 2007230(2)199-205
bull Irene C Boettcher1 Tanja Steinberg Kaspar Matiasek Craig E Greene Katrin Hartmann Andrea Fischer
CSF IgG was detected only in strongly seropositive cats suggested that CSF anti-coronavirus IgG was derived from blood Measurement of
anti-coronavirus IgG in CSF was of equivocal clinical use
Test test test
FCoV RT-PCR test ( bloodeffusion fluidfeces)
Blood FCoV RT-PCR FECV Monocyte-associated viremia Not differentiate FIPV from pathotype
FCoV
Fecal FCoV RT-PC Recommend for house-cat management BUT single positive or negative tests are
meaningless as cats may shed intermittently or may be recently infected
Effusion fluid FCoV RT-PCR bull Generally recommended for fluid bull Positive result high PPV bull But 30 of effusions from cats
with FIP may be negative by RT-PCR
Why false negative 1 FIPV is cell-associated and likely confined to cells of perivascular granuloma (leaking out of pure plasma) 2 Inhibition of RT-PCR by interfering substances in fluid Therefore negative result doesnrsquot exclude FIP
Is FIP a contagious disease (cat-to-cat transmission)
Is FIP a contagious disease (cat-to-cat transmission)
Cats with FIP do not excrete pathogenic FIPV
FECV in enterocytes
Is FIP contagious
Cats with FIP do not appear to be very contagious to cats coming in contact with
Every FIPV isolated from a group outbreak of FIP does NOT genetically identical in its 3c gene mutation
However FIPV is found in the feces of most cats with FIP
Mutation when FECV turns into FIPV
Internal mutation theory bull Genetic changes from FECV
to FIPV
bull Various types of mutation within OPFs 3 and 7
bull 20 of kittens infected with FECV will produce an FIP mutant
Horizontal (cat-to cat) bull Transmission of FIPV
mutants
bull cats with FIP are shedding the same FIPV in their feces
J Gen Virol 2010 Feb91(Pt 2)415-20 doi 101099vir0016485-0 Epub 2009 Nov 4
Feline infectious peritonitis insights into feline coronavirus
pathobiogenesis and epidemiology based on genetic analysis of the viral
3c gene Chang HW1 de Groot RJ Egberink HF Rottier PJ
helliphellipMost cats with FIP had no detectable intestinal feline coronaviruses (FCoVs) and
had seemingly cleared the primary FECV infection In those with detectable intestinal
FCoV the virus always had an intact 3c and seemed to have been acquired by FECV
superinfection Apparently 3c-inactivated viruses replicate not at all--or only poorly--in the
gut explaining the rare incidence of FIP outbreaks
FIP transmission
FIP transmission
bull Vet Res 2013 Jul 174457 doi 1011861297-9716-44-57
bull An outbreak of feline infectious peritonitis in a Taiwanese shelter epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus
bull Wang YT1 Su BL Hsieh LE Chueh LL
bull Abstract
bull helliphellipSequence analysis revealed that the type II FIPV detected from fecal samples body
effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death Taken together our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment
FCoV field strain in FIP cat
Genomic RNA sequence of feline coronavirus strain FCoV C1Je Charlotte Dye BVMampS PhD CertSAM MRCVS
Stuart G Siddell BSc(Hons) PhD
bull This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV) Viral RNAs isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP) derived 100 nucleotide identity
Feline Coronavirus serotypes I and II were reported in natural infection
bull Feline coronavirus serotypes 1 and 2 seroprevalence and association with disease in Switzerland
bull Clin Diagn Lab Immunol October 200512(10)1209-15 bull Maya Kummrow1 Marina L Meli Michael Haessig Enikoe Goenczi Amy Poland Niels C
Pedersen Regina Hofmann-Lehmann Hans Lutz
bull Comparison of serologic techniques for the detection of antibodies against feline coronaviruses
bull J Vet Diagn Invest January 200820(1)45-50 bull Annamaria Pratelli1
bull Prevalence of Korean cats with natural feline coronavirus infections bull Virol J January 20118(0)455 bull Dong-Jun An1 Hye-Young Jeoung Wooseog Jeong Jee Yong Park Myoung-Heon Lee Bong
Kyun Park bull 1National Veterinary Research and Quarantine Service Anyang Kyunggi-do430-824 Korea
bull Moreshellip
Take home message Knowing ME knowing YOU
My team my world
Thank you
Diagnosis of FIP A frustation
bull Clinical Examination and environmental consideration
bull Laboratory supports
bull Imaging findings
bull Cytology Serology and molecular diagnosis
bull Histopathological confirmation
What is the PROBLEM of FIP diagnosis
bull Sick cats presented with no effusion (pleural peritoneal cavity)
ldquo dry FIP ldquo
bull Normalhealthy shedder cats
Physical and Environmental findings
Multifactoral risk
bull Owner bull Multi-cat household
bull Cat bull Age blood line
bull Pure breeds gt DSH
bull Immune response
bull Virus bull Mutation
bull Uncertain period (exposed to clinically sick)
bull Environment bull Stress
bull Physical findings Depend on when the
cats are presented
ndash Early
ndash Mid
ndash Late
How does ldquoAGErdquo of sick cat help the diagnosis
Inc period 2-14 days (exprsquol) bull FCoV in feces found as
early as 2 days after exposure (main site is colon)
bull Clinical FIP found as early as 2 wk old to 18 months
and elderly gt 12 yr
bull From pyogranulomatous inflammation to clinical signs may be many months
How does ldquoAGErdquo of sick cat help the diagnosis
bull Pattern of virus nature
bull Pathogenesis of virulentnon virulent virus
bull Exposure time to clinical
sickness
bull Factors of immune response
bull Concurrent diseases
Inc period 2-14 days (exprsquol) bull FCoV in feces found as
early as 2 days after exposure (main site is colon)
bull Clinical FIP found as early as 2 wk old to 18 months
and elderly gt 12 yr
bull From pyogranulomatous inflammation to clinical signs may be many months
เรามาถงจดนไดอยางไร
Objective Knowing FCoVs
Clinical relationship of FCoVs FECV and FIPV
Feline coronavirus classification flowchart
A Kipar and M L Meli Vet Pathol 201451505-526
Copyright copy by American College of Veterinary Pathologists
Feline coronavirus classification flowchart
A Kipar and M L Meli Vet Pathol 201451505-526
Copyright copy by American College of Veterinary Pathologists
CCoV FCoV TGEV
bull All group 1 Coronavirus are antigenically related
bull FCoV is divided into 2 serotypes bull FCoV 1
bull FCoV 2
bull FCoV 2 is antigenically similar to CCoV
( FCoV 2 is a recombinant of FCoV and CCoV)
bull BUT most field-strains are FCoV 1
Genetic relationships between the different feline and canine
coronaviruses genotypes (FCoV CCoV and TGEV)
From wwwgooglecom
FCoVs ndashwho are they
FCoV I
FCoV II
2 serotypes
FCoVs ndashwho are they
FCoV I
FCoV II
2 serotypes
2 biotypes pathotypes
FECV
FIPV
Enteric biotype Virulent biotype
FECVFIPV -serologicalmorphological undistinguishable
Prevalence of Feline Coronaviruses (FCoV)
Housed cats
bull 25-40 of cats infected with FCoV
Multi cat household colonies
bull 80-100 of cats infected with FCoV
In high prevalent area occurrence of FIP ~ 10
How FECV turn into FIPV
bull Two theories
ndash Internal mutation
ndash Circulating virulent avirulent viruses
bull FIPV and FECV strains can be serotpye I or II
Mutation when FECV turns into FIPV
Internal mutation theory
bull Genetic changes from FECV to FIPV in individual infected cat
bull Various types of mutation within 3c gene
bull 20 of kittens infected with FECV will produce an FIP mutant
Molecular Studies for diagnosis of FIP
bull Conflicting results
bull FCoV 1 (FIPV I) hellipvirulent bull FCoV II (FIPV II)hellipnon-virulent
Pathogenesis of FIP controversial
bull Immune-mediated vasculitis
bull Immune complex Type 3 hypersensitivity disease
Ag + Ab +compliments +C3
bull Pathological morphology
ndash Activation of monocytes
macrophages
ndash Monocyte-mediated viremia
ndash Granulomatous phleblitis periphlebitis
ndash VEGF ndash mediators increase vascular permeability
Endothelial cells show strongly MHCII antigen positive
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Activated macrophages
Morphologic Features and Development of Granulomatous vasculitis in FIP Kipar et al(2005)
Emigration of FCoV ndashinfected monocytes to vascular perivascular granulomatous infiltrates
with destruction of vascular basal laminar
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Leptomeningeal veins Agglomerate of TNF-α-positive monocytes attached to
venous endothelium Avidin-biotin-peroxidase complex method Papanicolaous hematoxylin counterstain Bar = 10 μm
Objective bullKnowing FCoVs
bullFCoVs in clinical diagnosis
Serology and Molecular diagnosis
Indirect FCoV antibody test Direct (viral load) FCoV RT-PCR
bull Blood
bull Feces
bull Effusion fluid
bull CSF
bull At present NO nucleoprotein sequences unique to pathogenic FCoV (ie not also present in nonpathogenic FCoV) have been identified
FCoV FECV FCoV where are they
Small intestinal enterocytes
Colon -rectum
Healthy shedders
Asymptomatic or mild diarrhea
After clearance from sm intestine FCoVs spread to infect colon and intermittently shedded off
If kittens infected before immune system fully mature levels of FECV replication will be very high
Reinfection may be from FCoV same strains or different strains
Pyogranulomatous inflammation
FIPV infected monocytes perivascular macrophages overproduce neutrophil survival factors Tumor necrosis factor- alpha (TNF ndashalpha) bull Matrix metalloproyeinase-9 bull GM-CSF bull G-CSF Neutrophil survival Development of granuloma lesions
Interpretation of FCoV antibody test
Viral shedding ~ 2 days (FCoV in epithelial cells)
Signs of FIP
bull As early as 2 wk old to 18 months
bull From pyogranulomatous inflammation to clinical signs may be months
From NC Pederson et al (2008) Feline enteric coronavirus infection
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To rule out FIP in sick cats bull effusive FIP
bull non- effusive FIP ( esp cats with GI signs)
bull To screen the FCoV excretors bull Cats in contact with known FCoV shedder
bull Cats in the household
bull New kitten or new cat bringing into the multi-cat household
bull Before receiving immunosuppressive treatment or stressful procedures
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To screen a breeding queen
bull To monitor FIP treatment q 8-12 wks
bull To screen blood donor cat
bull To screen prior to FeLV vaccination
Blood fluid Interpretation of FCoV antibody test
I false negative in sick FIP cat
II High titer (gt 11600) in normal cat (esp cat from multi-household) is not indicated FIP
III High titer in fluid high PPV
IV Generally not recommended in sick cat
FCoV antibody in CSF
bull Use of anti-coronavirus antibody testing of cerebrospinal fluid for diagnosis of feline infectious peritonitis involving the central nervous system in cats
bull J Am Vet Med Assoc January 2007230(2)199-205
bull Irene C Boettcher1 Tanja Steinberg Kaspar Matiasek Craig E Greene Katrin Hartmann Andrea Fischer
CSF IgG was detected only in strongly seropositive cats suggested that CSF anti-coronavirus IgG was derived from blood Measurement of
anti-coronavirus IgG in CSF was of equivocal clinical use
Test test test
FCoV RT-PCR test ( bloodeffusion fluidfeces)
Blood FCoV RT-PCR FECV Monocyte-associated viremia Not differentiate FIPV from pathotype
FCoV
Fecal FCoV RT-PC Recommend for house-cat management BUT single positive or negative tests are
meaningless as cats may shed intermittently or may be recently infected
Effusion fluid FCoV RT-PCR bull Generally recommended for fluid bull Positive result high PPV bull But 30 of effusions from cats
with FIP may be negative by RT-PCR
Why false negative 1 FIPV is cell-associated and likely confined to cells of perivascular granuloma (leaking out of pure plasma) 2 Inhibition of RT-PCR by interfering substances in fluid Therefore negative result doesnrsquot exclude FIP
Is FIP a contagious disease (cat-to-cat transmission)
Is FIP a contagious disease (cat-to-cat transmission)
Cats with FIP do not excrete pathogenic FIPV
FECV in enterocytes
Is FIP contagious
Cats with FIP do not appear to be very contagious to cats coming in contact with
Every FIPV isolated from a group outbreak of FIP does NOT genetically identical in its 3c gene mutation
However FIPV is found in the feces of most cats with FIP
Mutation when FECV turns into FIPV
Internal mutation theory bull Genetic changes from FECV
to FIPV
bull Various types of mutation within OPFs 3 and 7
bull 20 of kittens infected with FECV will produce an FIP mutant
Horizontal (cat-to cat) bull Transmission of FIPV
mutants
bull cats with FIP are shedding the same FIPV in their feces
J Gen Virol 2010 Feb91(Pt 2)415-20 doi 101099vir0016485-0 Epub 2009 Nov 4
Feline infectious peritonitis insights into feline coronavirus
pathobiogenesis and epidemiology based on genetic analysis of the viral
3c gene Chang HW1 de Groot RJ Egberink HF Rottier PJ
helliphellipMost cats with FIP had no detectable intestinal feline coronaviruses (FCoVs) and
had seemingly cleared the primary FECV infection In those with detectable intestinal
FCoV the virus always had an intact 3c and seemed to have been acquired by FECV
superinfection Apparently 3c-inactivated viruses replicate not at all--or only poorly--in the
gut explaining the rare incidence of FIP outbreaks
FIP transmission
FIP transmission
bull Vet Res 2013 Jul 174457 doi 1011861297-9716-44-57
bull An outbreak of feline infectious peritonitis in a Taiwanese shelter epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus
bull Wang YT1 Su BL Hsieh LE Chueh LL
bull Abstract
bull helliphellipSequence analysis revealed that the type II FIPV detected from fecal samples body
effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death Taken together our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment
FCoV field strain in FIP cat
Genomic RNA sequence of feline coronavirus strain FCoV C1Je Charlotte Dye BVMampS PhD CertSAM MRCVS
Stuart G Siddell BSc(Hons) PhD
bull This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV) Viral RNAs isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP) derived 100 nucleotide identity
Feline Coronavirus serotypes I and II were reported in natural infection
bull Feline coronavirus serotypes 1 and 2 seroprevalence and association with disease in Switzerland
bull Clin Diagn Lab Immunol October 200512(10)1209-15 bull Maya Kummrow1 Marina L Meli Michael Haessig Enikoe Goenczi Amy Poland Niels C
Pedersen Regina Hofmann-Lehmann Hans Lutz
bull Comparison of serologic techniques for the detection of antibodies against feline coronaviruses
bull J Vet Diagn Invest January 200820(1)45-50 bull Annamaria Pratelli1
bull Prevalence of Korean cats with natural feline coronavirus infections bull Virol J January 20118(0)455 bull Dong-Jun An1 Hye-Young Jeoung Wooseog Jeong Jee Yong Park Myoung-Heon Lee Bong
Kyun Park bull 1National Veterinary Research and Quarantine Service Anyang Kyunggi-do430-824 Korea
bull Moreshellip
Take home message Knowing ME knowing YOU
My team my world
Thank you
What is the PROBLEM of FIP diagnosis
bull Sick cats presented with no effusion (pleural peritoneal cavity)
ldquo dry FIP ldquo
bull Normalhealthy shedder cats
Physical and Environmental findings
Multifactoral risk
bull Owner bull Multi-cat household
bull Cat bull Age blood line
bull Pure breeds gt DSH
bull Immune response
bull Virus bull Mutation
bull Uncertain period (exposed to clinically sick)
bull Environment bull Stress
bull Physical findings Depend on when the
cats are presented
ndash Early
ndash Mid
ndash Late
How does ldquoAGErdquo of sick cat help the diagnosis
Inc period 2-14 days (exprsquol) bull FCoV in feces found as
early as 2 days after exposure (main site is colon)
bull Clinical FIP found as early as 2 wk old to 18 months
and elderly gt 12 yr
bull From pyogranulomatous inflammation to clinical signs may be many months
How does ldquoAGErdquo of sick cat help the diagnosis
bull Pattern of virus nature
bull Pathogenesis of virulentnon virulent virus
bull Exposure time to clinical
sickness
bull Factors of immune response
bull Concurrent diseases
Inc period 2-14 days (exprsquol) bull FCoV in feces found as
early as 2 days after exposure (main site is colon)
bull Clinical FIP found as early as 2 wk old to 18 months
and elderly gt 12 yr
bull From pyogranulomatous inflammation to clinical signs may be many months
เรามาถงจดนไดอยางไร
Objective Knowing FCoVs
Clinical relationship of FCoVs FECV and FIPV
Feline coronavirus classification flowchart
A Kipar and M L Meli Vet Pathol 201451505-526
Copyright copy by American College of Veterinary Pathologists
Feline coronavirus classification flowchart
A Kipar and M L Meli Vet Pathol 201451505-526
Copyright copy by American College of Veterinary Pathologists
CCoV FCoV TGEV
bull All group 1 Coronavirus are antigenically related
bull FCoV is divided into 2 serotypes bull FCoV 1
bull FCoV 2
bull FCoV 2 is antigenically similar to CCoV
( FCoV 2 is a recombinant of FCoV and CCoV)
bull BUT most field-strains are FCoV 1
Genetic relationships between the different feline and canine
coronaviruses genotypes (FCoV CCoV and TGEV)
From wwwgooglecom
FCoVs ndashwho are they
FCoV I
FCoV II
2 serotypes
FCoVs ndashwho are they
FCoV I
FCoV II
2 serotypes
2 biotypes pathotypes
FECV
FIPV
Enteric biotype Virulent biotype
FECVFIPV -serologicalmorphological undistinguishable
Prevalence of Feline Coronaviruses (FCoV)
Housed cats
bull 25-40 of cats infected with FCoV
Multi cat household colonies
bull 80-100 of cats infected with FCoV
In high prevalent area occurrence of FIP ~ 10
How FECV turn into FIPV
bull Two theories
ndash Internal mutation
ndash Circulating virulent avirulent viruses
bull FIPV and FECV strains can be serotpye I or II
Mutation when FECV turns into FIPV
Internal mutation theory
bull Genetic changes from FECV to FIPV in individual infected cat
bull Various types of mutation within 3c gene
bull 20 of kittens infected with FECV will produce an FIP mutant
Molecular Studies for diagnosis of FIP
bull Conflicting results
bull FCoV 1 (FIPV I) hellipvirulent bull FCoV II (FIPV II)hellipnon-virulent
Pathogenesis of FIP controversial
bull Immune-mediated vasculitis
bull Immune complex Type 3 hypersensitivity disease
Ag + Ab +compliments +C3
bull Pathological morphology
ndash Activation of monocytes
macrophages
ndash Monocyte-mediated viremia
ndash Granulomatous phleblitis periphlebitis
ndash VEGF ndash mediators increase vascular permeability
Endothelial cells show strongly MHCII antigen positive
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Activated macrophages
Morphologic Features and Development of Granulomatous vasculitis in FIP Kipar et al(2005)
Emigration of FCoV ndashinfected monocytes to vascular perivascular granulomatous infiltrates
with destruction of vascular basal laminar
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Leptomeningeal veins Agglomerate of TNF-α-positive monocytes attached to
venous endothelium Avidin-biotin-peroxidase complex method Papanicolaous hematoxylin counterstain Bar = 10 μm
Objective bullKnowing FCoVs
bullFCoVs in clinical diagnosis
Serology and Molecular diagnosis
Indirect FCoV antibody test Direct (viral load) FCoV RT-PCR
bull Blood
bull Feces
bull Effusion fluid
bull CSF
bull At present NO nucleoprotein sequences unique to pathogenic FCoV (ie not also present in nonpathogenic FCoV) have been identified
FCoV FECV FCoV where are they
Small intestinal enterocytes
Colon -rectum
Healthy shedders
Asymptomatic or mild diarrhea
After clearance from sm intestine FCoVs spread to infect colon and intermittently shedded off
If kittens infected before immune system fully mature levels of FECV replication will be very high
Reinfection may be from FCoV same strains or different strains
Pyogranulomatous inflammation
FIPV infected monocytes perivascular macrophages overproduce neutrophil survival factors Tumor necrosis factor- alpha (TNF ndashalpha) bull Matrix metalloproyeinase-9 bull GM-CSF bull G-CSF Neutrophil survival Development of granuloma lesions
Interpretation of FCoV antibody test
Viral shedding ~ 2 days (FCoV in epithelial cells)
Signs of FIP
bull As early as 2 wk old to 18 months
bull From pyogranulomatous inflammation to clinical signs may be months
From NC Pederson et al (2008) Feline enteric coronavirus infection
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To rule out FIP in sick cats bull effusive FIP
bull non- effusive FIP ( esp cats with GI signs)
bull To screen the FCoV excretors bull Cats in contact with known FCoV shedder
bull Cats in the household
bull New kitten or new cat bringing into the multi-cat household
bull Before receiving immunosuppressive treatment or stressful procedures
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To screen a breeding queen
bull To monitor FIP treatment q 8-12 wks
bull To screen blood donor cat
bull To screen prior to FeLV vaccination
Blood fluid Interpretation of FCoV antibody test
I false negative in sick FIP cat
II High titer (gt 11600) in normal cat (esp cat from multi-household) is not indicated FIP
III High titer in fluid high PPV
IV Generally not recommended in sick cat
FCoV antibody in CSF
bull Use of anti-coronavirus antibody testing of cerebrospinal fluid for diagnosis of feline infectious peritonitis involving the central nervous system in cats
bull J Am Vet Med Assoc January 2007230(2)199-205
bull Irene C Boettcher1 Tanja Steinberg Kaspar Matiasek Craig E Greene Katrin Hartmann Andrea Fischer
CSF IgG was detected only in strongly seropositive cats suggested that CSF anti-coronavirus IgG was derived from blood Measurement of
anti-coronavirus IgG in CSF was of equivocal clinical use
Test test test
FCoV RT-PCR test ( bloodeffusion fluidfeces)
Blood FCoV RT-PCR FECV Monocyte-associated viremia Not differentiate FIPV from pathotype
FCoV
Fecal FCoV RT-PC Recommend for house-cat management BUT single positive or negative tests are
meaningless as cats may shed intermittently or may be recently infected
Effusion fluid FCoV RT-PCR bull Generally recommended for fluid bull Positive result high PPV bull But 30 of effusions from cats
with FIP may be negative by RT-PCR
Why false negative 1 FIPV is cell-associated and likely confined to cells of perivascular granuloma (leaking out of pure plasma) 2 Inhibition of RT-PCR by interfering substances in fluid Therefore negative result doesnrsquot exclude FIP
Is FIP a contagious disease (cat-to-cat transmission)
Is FIP a contagious disease (cat-to-cat transmission)
Cats with FIP do not excrete pathogenic FIPV
FECV in enterocytes
Is FIP contagious
Cats with FIP do not appear to be very contagious to cats coming in contact with
Every FIPV isolated from a group outbreak of FIP does NOT genetically identical in its 3c gene mutation
However FIPV is found in the feces of most cats with FIP
Mutation when FECV turns into FIPV
Internal mutation theory bull Genetic changes from FECV
to FIPV
bull Various types of mutation within OPFs 3 and 7
bull 20 of kittens infected with FECV will produce an FIP mutant
Horizontal (cat-to cat) bull Transmission of FIPV
mutants
bull cats with FIP are shedding the same FIPV in their feces
J Gen Virol 2010 Feb91(Pt 2)415-20 doi 101099vir0016485-0 Epub 2009 Nov 4
Feline infectious peritonitis insights into feline coronavirus
pathobiogenesis and epidemiology based on genetic analysis of the viral
3c gene Chang HW1 de Groot RJ Egberink HF Rottier PJ
helliphellipMost cats with FIP had no detectable intestinal feline coronaviruses (FCoVs) and
had seemingly cleared the primary FECV infection In those with detectable intestinal
FCoV the virus always had an intact 3c and seemed to have been acquired by FECV
superinfection Apparently 3c-inactivated viruses replicate not at all--or only poorly--in the
gut explaining the rare incidence of FIP outbreaks
FIP transmission
FIP transmission
bull Vet Res 2013 Jul 174457 doi 1011861297-9716-44-57
bull An outbreak of feline infectious peritonitis in a Taiwanese shelter epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus
bull Wang YT1 Su BL Hsieh LE Chueh LL
bull Abstract
bull helliphellipSequence analysis revealed that the type II FIPV detected from fecal samples body
effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death Taken together our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment
FCoV field strain in FIP cat
Genomic RNA sequence of feline coronavirus strain FCoV C1Je Charlotte Dye BVMampS PhD CertSAM MRCVS
Stuart G Siddell BSc(Hons) PhD
bull This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV) Viral RNAs isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP) derived 100 nucleotide identity
Feline Coronavirus serotypes I and II were reported in natural infection
bull Feline coronavirus serotypes 1 and 2 seroprevalence and association with disease in Switzerland
bull Clin Diagn Lab Immunol October 200512(10)1209-15 bull Maya Kummrow1 Marina L Meli Michael Haessig Enikoe Goenczi Amy Poland Niels C
Pedersen Regina Hofmann-Lehmann Hans Lutz
bull Comparison of serologic techniques for the detection of antibodies against feline coronaviruses
bull J Vet Diagn Invest January 200820(1)45-50 bull Annamaria Pratelli1
bull Prevalence of Korean cats with natural feline coronavirus infections bull Virol J January 20118(0)455 bull Dong-Jun An1 Hye-Young Jeoung Wooseog Jeong Jee Yong Park Myoung-Heon Lee Bong
Kyun Park bull 1National Veterinary Research and Quarantine Service Anyang Kyunggi-do430-824 Korea
bull Moreshellip
Take home message Knowing ME knowing YOU
My team my world
Thank you
Physical and Environmental findings
Multifactoral risk
bull Owner bull Multi-cat household
bull Cat bull Age blood line
bull Pure breeds gt DSH
bull Immune response
bull Virus bull Mutation
bull Uncertain period (exposed to clinically sick)
bull Environment bull Stress
bull Physical findings Depend on when the
cats are presented
ndash Early
ndash Mid
ndash Late
How does ldquoAGErdquo of sick cat help the diagnosis
Inc period 2-14 days (exprsquol) bull FCoV in feces found as
early as 2 days after exposure (main site is colon)
bull Clinical FIP found as early as 2 wk old to 18 months
and elderly gt 12 yr
bull From pyogranulomatous inflammation to clinical signs may be many months
How does ldquoAGErdquo of sick cat help the diagnosis
bull Pattern of virus nature
bull Pathogenesis of virulentnon virulent virus
bull Exposure time to clinical
sickness
bull Factors of immune response
bull Concurrent diseases
Inc period 2-14 days (exprsquol) bull FCoV in feces found as
early as 2 days after exposure (main site is colon)
bull Clinical FIP found as early as 2 wk old to 18 months
and elderly gt 12 yr
bull From pyogranulomatous inflammation to clinical signs may be many months
เรามาถงจดนไดอยางไร
Objective Knowing FCoVs
Clinical relationship of FCoVs FECV and FIPV
Feline coronavirus classification flowchart
A Kipar and M L Meli Vet Pathol 201451505-526
Copyright copy by American College of Veterinary Pathologists
Feline coronavirus classification flowchart
A Kipar and M L Meli Vet Pathol 201451505-526
Copyright copy by American College of Veterinary Pathologists
CCoV FCoV TGEV
bull All group 1 Coronavirus are antigenically related
bull FCoV is divided into 2 serotypes bull FCoV 1
bull FCoV 2
bull FCoV 2 is antigenically similar to CCoV
( FCoV 2 is a recombinant of FCoV and CCoV)
bull BUT most field-strains are FCoV 1
Genetic relationships between the different feline and canine
coronaviruses genotypes (FCoV CCoV and TGEV)
From wwwgooglecom
FCoVs ndashwho are they
FCoV I
FCoV II
2 serotypes
FCoVs ndashwho are they
FCoV I
FCoV II
2 serotypes
2 biotypes pathotypes
FECV
FIPV
Enteric biotype Virulent biotype
FECVFIPV -serologicalmorphological undistinguishable
Prevalence of Feline Coronaviruses (FCoV)
Housed cats
bull 25-40 of cats infected with FCoV
Multi cat household colonies
bull 80-100 of cats infected with FCoV
In high prevalent area occurrence of FIP ~ 10
How FECV turn into FIPV
bull Two theories
ndash Internal mutation
ndash Circulating virulent avirulent viruses
bull FIPV and FECV strains can be serotpye I or II
Mutation when FECV turns into FIPV
Internal mutation theory
bull Genetic changes from FECV to FIPV in individual infected cat
bull Various types of mutation within 3c gene
bull 20 of kittens infected with FECV will produce an FIP mutant
Molecular Studies for diagnosis of FIP
bull Conflicting results
bull FCoV 1 (FIPV I) hellipvirulent bull FCoV II (FIPV II)hellipnon-virulent
Pathogenesis of FIP controversial
bull Immune-mediated vasculitis
bull Immune complex Type 3 hypersensitivity disease
Ag + Ab +compliments +C3
bull Pathological morphology
ndash Activation of monocytes
macrophages
ndash Monocyte-mediated viremia
ndash Granulomatous phleblitis periphlebitis
ndash VEGF ndash mediators increase vascular permeability
Endothelial cells show strongly MHCII antigen positive
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Activated macrophages
Morphologic Features and Development of Granulomatous vasculitis in FIP Kipar et al(2005)
Emigration of FCoV ndashinfected monocytes to vascular perivascular granulomatous infiltrates
with destruction of vascular basal laminar
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Leptomeningeal veins Agglomerate of TNF-α-positive monocytes attached to
venous endothelium Avidin-biotin-peroxidase complex method Papanicolaous hematoxylin counterstain Bar = 10 μm
Objective bullKnowing FCoVs
bullFCoVs in clinical diagnosis
Serology and Molecular diagnosis
Indirect FCoV antibody test Direct (viral load) FCoV RT-PCR
bull Blood
bull Feces
bull Effusion fluid
bull CSF
bull At present NO nucleoprotein sequences unique to pathogenic FCoV (ie not also present in nonpathogenic FCoV) have been identified
FCoV FECV FCoV where are they
Small intestinal enterocytes
Colon -rectum
Healthy shedders
Asymptomatic or mild diarrhea
After clearance from sm intestine FCoVs spread to infect colon and intermittently shedded off
If kittens infected before immune system fully mature levels of FECV replication will be very high
Reinfection may be from FCoV same strains or different strains
Pyogranulomatous inflammation
FIPV infected monocytes perivascular macrophages overproduce neutrophil survival factors Tumor necrosis factor- alpha (TNF ndashalpha) bull Matrix metalloproyeinase-9 bull GM-CSF bull G-CSF Neutrophil survival Development of granuloma lesions
Interpretation of FCoV antibody test
Viral shedding ~ 2 days (FCoV in epithelial cells)
Signs of FIP
bull As early as 2 wk old to 18 months
bull From pyogranulomatous inflammation to clinical signs may be months
From NC Pederson et al (2008) Feline enteric coronavirus infection
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To rule out FIP in sick cats bull effusive FIP
bull non- effusive FIP ( esp cats with GI signs)
bull To screen the FCoV excretors bull Cats in contact with known FCoV shedder
bull Cats in the household
bull New kitten or new cat bringing into the multi-cat household
bull Before receiving immunosuppressive treatment or stressful procedures
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To screen a breeding queen
bull To monitor FIP treatment q 8-12 wks
bull To screen blood donor cat
bull To screen prior to FeLV vaccination
Blood fluid Interpretation of FCoV antibody test
I false negative in sick FIP cat
II High titer (gt 11600) in normal cat (esp cat from multi-household) is not indicated FIP
III High titer in fluid high PPV
IV Generally not recommended in sick cat
FCoV antibody in CSF
bull Use of anti-coronavirus antibody testing of cerebrospinal fluid for diagnosis of feline infectious peritonitis involving the central nervous system in cats
bull J Am Vet Med Assoc January 2007230(2)199-205
bull Irene C Boettcher1 Tanja Steinberg Kaspar Matiasek Craig E Greene Katrin Hartmann Andrea Fischer
CSF IgG was detected only in strongly seropositive cats suggested that CSF anti-coronavirus IgG was derived from blood Measurement of
anti-coronavirus IgG in CSF was of equivocal clinical use
Test test test
FCoV RT-PCR test ( bloodeffusion fluidfeces)
Blood FCoV RT-PCR FECV Monocyte-associated viremia Not differentiate FIPV from pathotype
FCoV
Fecal FCoV RT-PC Recommend for house-cat management BUT single positive or negative tests are
meaningless as cats may shed intermittently or may be recently infected
Effusion fluid FCoV RT-PCR bull Generally recommended for fluid bull Positive result high PPV bull But 30 of effusions from cats
with FIP may be negative by RT-PCR
Why false negative 1 FIPV is cell-associated and likely confined to cells of perivascular granuloma (leaking out of pure plasma) 2 Inhibition of RT-PCR by interfering substances in fluid Therefore negative result doesnrsquot exclude FIP
Is FIP a contagious disease (cat-to-cat transmission)
Is FIP a contagious disease (cat-to-cat transmission)
Cats with FIP do not excrete pathogenic FIPV
FECV in enterocytes
Is FIP contagious
Cats with FIP do not appear to be very contagious to cats coming in contact with
Every FIPV isolated from a group outbreak of FIP does NOT genetically identical in its 3c gene mutation
However FIPV is found in the feces of most cats with FIP
Mutation when FECV turns into FIPV
Internal mutation theory bull Genetic changes from FECV
to FIPV
bull Various types of mutation within OPFs 3 and 7
bull 20 of kittens infected with FECV will produce an FIP mutant
Horizontal (cat-to cat) bull Transmission of FIPV
mutants
bull cats with FIP are shedding the same FIPV in their feces
J Gen Virol 2010 Feb91(Pt 2)415-20 doi 101099vir0016485-0 Epub 2009 Nov 4
Feline infectious peritonitis insights into feline coronavirus
pathobiogenesis and epidemiology based on genetic analysis of the viral
3c gene Chang HW1 de Groot RJ Egberink HF Rottier PJ
helliphellipMost cats with FIP had no detectable intestinal feline coronaviruses (FCoVs) and
had seemingly cleared the primary FECV infection In those with detectable intestinal
FCoV the virus always had an intact 3c and seemed to have been acquired by FECV
superinfection Apparently 3c-inactivated viruses replicate not at all--or only poorly--in the
gut explaining the rare incidence of FIP outbreaks
FIP transmission
FIP transmission
bull Vet Res 2013 Jul 174457 doi 1011861297-9716-44-57
bull An outbreak of feline infectious peritonitis in a Taiwanese shelter epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus
bull Wang YT1 Su BL Hsieh LE Chueh LL
bull Abstract
bull helliphellipSequence analysis revealed that the type II FIPV detected from fecal samples body
effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death Taken together our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment
FCoV field strain in FIP cat
Genomic RNA sequence of feline coronavirus strain FCoV C1Je Charlotte Dye BVMampS PhD CertSAM MRCVS
Stuart G Siddell BSc(Hons) PhD
bull This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV) Viral RNAs isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP) derived 100 nucleotide identity
Feline Coronavirus serotypes I and II were reported in natural infection
bull Feline coronavirus serotypes 1 and 2 seroprevalence and association with disease in Switzerland
bull Clin Diagn Lab Immunol October 200512(10)1209-15 bull Maya Kummrow1 Marina L Meli Michael Haessig Enikoe Goenczi Amy Poland Niels C
Pedersen Regina Hofmann-Lehmann Hans Lutz
bull Comparison of serologic techniques for the detection of antibodies against feline coronaviruses
bull J Vet Diagn Invest January 200820(1)45-50 bull Annamaria Pratelli1
bull Prevalence of Korean cats with natural feline coronavirus infections bull Virol J January 20118(0)455 bull Dong-Jun An1 Hye-Young Jeoung Wooseog Jeong Jee Yong Park Myoung-Heon Lee Bong
Kyun Park bull 1National Veterinary Research and Quarantine Service Anyang Kyunggi-do430-824 Korea
bull Moreshellip
Take home message Knowing ME knowing YOU
My team my world
Thank you
How does ldquoAGErdquo of sick cat help the diagnosis
Inc period 2-14 days (exprsquol) bull FCoV in feces found as
early as 2 days after exposure (main site is colon)
bull Clinical FIP found as early as 2 wk old to 18 months
and elderly gt 12 yr
bull From pyogranulomatous inflammation to clinical signs may be many months
How does ldquoAGErdquo of sick cat help the diagnosis
bull Pattern of virus nature
bull Pathogenesis of virulentnon virulent virus
bull Exposure time to clinical
sickness
bull Factors of immune response
bull Concurrent diseases
Inc period 2-14 days (exprsquol) bull FCoV in feces found as
early as 2 days after exposure (main site is colon)
bull Clinical FIP found as early as 2 wk old to 18 months
and elderly gt 12 yr
bull From pyogranulomatous inflammation to clinical signs may be many months
เรามาถงจดนไดอยางไร
Objective Knowing FCoVs
Clinical relationship of FCoVs FECV and FIPV
Feline coronavirus classification flowchart
A Kipar and M L Meli Vet Pathol 201451505-526
Copyright copy by American College of Veterinary Pathologists
Feline coronavirus classification flowchart
A Kipar and M L Meli Vet Pathol 201451505-526
Copyright copy by American College of Veterinary Pathologists
CCoV FCoV TGEV
bull All group 1 Coronavirus are antigenically related
bull FCoV is divided into 2 serotypes bull FCoV 1
bull FCoV 2
bull FCoV 2 is antigenically similar to CCoV
( FCoV 2 is a recombinant of FCoV and CCoV)
bull BUT most field-strains are FCoV 1
Genetic relationships between the different feline and canine
coronaviruses genotypes (FCoV CCoV and TGEV)
From wwwgooglecom
FCoVs ndashwho are they
FCoV I
FCoV II
2 serotypes
FCoVs ndashwho are they
FCoV I
FCoV II
2 serotypes
2 biotypes pathotypes
FECV
FIPV
Enteric biotype Virulent biotype
FECVFIPV -serologicalmorphological undistinguishable
Prevalence of Feline Coronaviruses (FCoV)
Housed cats
bull 25-40 of cats infected with FCoV
Multi cat household colonies
bull 80-100 of cats infected with FCoV
In high prevalent area occurrence of FIP ~ 10
How FECV turn into FIPV
bull Two theories
ndash Internal mutation
ndash Circulating virulent avirulent viruses
bull FIPV and FECV strains can be serotpye I or II
Mutation when FECV turns into FIPV
Internal mutation theory
bull Genetic changes from FECV to FIPV in individual infected cat
bull Various types of mutation within 3c gene
bull 20 of kittens infected with FECV will produce an FIP mutant
Molecular Studies for diagnosis of FIP
bull Conflicting results
bull FCoV 1 (FIPV I) hellipvirulent bull FCoV II (FIPV II)hellipnon-virulent
Pathogenesis of FIP controversial
bull Immune-mediated vasculitis
bull Immune complex Type 3 hypersensitivity disease
Ag + Ab +compliments +C3
bull Pathological morphology
ndash Activation of monocytes
macrophages
ndash Monocyte-mediated viremia
ndash Granulomatous phleblitis periphlebitis
ndash VEGF ndash mediators increase vascular permeability
Endothelial cells show strongly MHCII antigen positive
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Activated macrophages
Morphologic Features and Development of Granulomatous vasculitis in FIP Kipar et al(2005)
Emigration of FCoV ndashinfected monocytes to vascular perivascular granulomatous infiltrates
with destruction of vascular basal laminar
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Leptomeningeal veins Agglomerate of TNF-α-positive monocytes attached to
venous endothelium Avidin-biotin-peroxidase complex method Papanicolaous hematoxylin counterstain Bar = 10 μm
Objective bullKnowing FCoVs
bullFCoVs in clinical diagnosis
Serology and Molecular diagnosis
Indirect FCoV antibody test Direct (viral load) FCoV RT-PCR
bull Blood
bull Feces
bull Effusion fluid
bull CSF
bull At present NO nucleoprotein sequences unique to pathogenic FCoV (ie not also present in nonpathogenic FCoV) have been identified
FCoV FECV FCoV where are they
Small intestinal enterocytes
Colon -rectum
Healthy shedders
Asymptomatic or mild diarrhea
After clearance from sm intestine FCoVs spread to infect colon and intermittently shedded off
If kittens infected before immune system fully mature levels of FECV replication will be very high
Reinfection may be from FCoV same strains or different strains
Pyogranulomatous inflammation
FIPV infected monocytes perivascular macrophages overproduce neutrophil survival factors Tumor necrosis factor- alpha (TNF ndashalpha) bull Matrix metalloproyeinase-9 bull GM-CSF bull G-CSF Neutrophil survival Development of granuloma lesions
Interpretation of FCoV antibody test
Viral shedding ~ 2 days (FCoV in epithelial cells)
Signs of FIP
bull As early as 2 wk old to 18 months
bull From pyogranulomatous inflammation to clinical signs may be months
From NC Pederson et al (2008) Feline enteric coronavirus infection
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To rule out FIP in sick cats bull effusive FIP
bull non- effusive FIP ( esp cats with GI signs)
bull To screen the FCoV excretors bull Cats in contact with known FCoV shedder
bull Cats in the household
bull New kitten or new cat bringing into the multi-cat household
bull Before receiving immunosuppressive treatment or stressful procedures
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To screen a breeding queen
bull To monitor FIP treatment q 8-12 wks
bull To screen blood donor cat
bull To screen prior to FeLV vaccination
Blood fluid Interpretation of FCoV antibody test
I false negative in sick FIP cat
II High titer (gt 11600) in normal cat (esp cat from multi-household) is not indicated FIP
III High titer in fluid high PPV
IV Generally not recommended in sick cat
FCoV antibody in CSF
bull Use of anti-coronavirus antibody testing of cerebrospinal fluid for diagnosis of feline infectious peritonitis involving the central nervous system in cats
bull J Am Vet Med Assoc January 2007230(2)199-205
bull Irene C Boettcher1 Tanja Steinberg Kaspar Matiasek Craig E Greene Katrin Hartmann Andrea Fischer
CSF IgG was detected only in strongly seropositive cats suggested that CSF anti-coronavirus IgG was derived from blood Measurement of
anti-coronavirus IgG in CSF was of equivocal clinical use
Test test test
FCoV RT-PCR test ( bloodeffusion fluidfeces)
Blood FCoV RT-PCR FECV Monocyte-associated viremia Not differentiate FIPV from pathotype
FCoV
Fecal FCoV RT-PC Recommend for house-cat management BUT single positive or negative tests are
meaningless as cats may shed intermittently or may be recently infected
Effusion fluid FCoV RT-PCR bull Generally recommended for fluid bull Positive result high PPV bull But 30 of effusions from cats
with FIP may be negative by RT-PCR
Why false negative 1 FIPV is cell-associated and likely confined to cells of perivascular granuloma (leaking out of pure plasma) 2 Inhibition of RT-PCR by interfering substances in fluid Therefore negative result doesnrsquot exclude FIP
Is FIP a contagious disease (cat-to-cat transmission)
Is FIP a contagious disease (cat-to-cat transmission)
Cats with FIP do not excrete pathogenic FIPV
FECV in enterocytes
Is FIP contagious
Cats with FIP do not appear to be very contagious to cats coming in contact with
Every FIPV isolated from a group outbreak of FIP does NOT genetically identical in its 3c gene mutation
However FIPV is found in the feces of most cats with FIP
Mutation when FECV turns into FIPV
Internal mutation theory bull Genetic changes from FECV
to FIPV
bull Various types of mutation within OPFs 3 and 7
bull 20 of kittens infected with FECV will produce an FIP mutant
Horizontal (cat-to cat) bull Transmission of FIPV
mutants
bull cats with FIP are shedding the same FIPV in their feces
J Gen Virol 2010 Feb91(Pt 2)415-20 doi 101099vir0016485-0 Epub 2009 Nov 4
Feline infectious peritonitis insights into feline coronavirus
pathobiogenesis and epidemiology based on genetic analysis of the viral
3c gene Chang HW1 de Groot RJ Egberink HF Rottier PJ
helliphellipMost cats with FIP had no detectable intestinal feline coronaviruses (FCoVs) and
had seemingly cleared the primary FECV infection In those with detectable intestinal
FCoV the virus always had an intact 3c and seemed to have been acquired by FECV
superinfection Apparently 3c-inactivated viruses replicate not at all--or only poorly--in the
gut explaining the rare incidence of FIP outbreaks
FIP transmission
FIP transmission
bull Vet Res 2013 Jul 174457 doi 1011861297-9716-44-57
bull An outbreak of feline infectious peritonitis in a Taiwanese shelter epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus
bull Wang YT1 Su BL Hsieh LE Chueh LL
bull Abstract
bull helliphellipSequence analysis revealed that the type II FIPV detected from fecal samples body
effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death Taken together our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment
FCoV field strain in FIP cat
Genomic RNA sequence of feline coronavirus strain FCoV C1Je Charlotte Dye BVMampS PhD CertSAM MRCVS
Stuart G Siddell BSc(Hons) PhD
bull This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV) Viral RNAs isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP) derived 100 nucleotide identity
Feline Coronavirus serotypes I and II were reported in natural infection
bull Feline coronavirus serotypes 1 and 2 seroprevalence and association with disease in Switzerland
bull Clin Diagn Lab Immunol October 200512(10)1209-15 bull Maya Kummrow1 Marina L Meli Michael Haessig Enikoe Goenczi Amy Poland Niels C
Pedersen Regina Hofmann-Lehmann Hans Lutz
bull Comparison of serologic techniques for the detection of antibodies against feline coronaviruses
bull J Vet Diagn Invest January 200820(1)45-50 bull Annamaria Pratelli1
bull Prevalence of Korean cats with natural feline coronavirus infections bull Virol J January 20118(0)455 bull Dong-Jun An1 Hye-Young Jeoung Wooseog Jeong Jee Yong Park Myoung-Heon Lee Bong
Kyun Park bull 1National Veterinary Research and Quarantine Service Anyang Kyunggi-do430-824 Korea
bull Moreshellip
Take home message Knowing ME knowing YOU
My team my world
Thank you
How does ldquoAGErdquo of sick cat help the diagnosis
bull Pattern of virus nature
bull Pathogenesis of virulentnon virulent virus
bull Exposure time to clinical
sickness
bull Factors of immune response
bull Concurrent diseases
Inc period 2-14 days (exprsquol) bull FCoV in feces found as
early as 2 days after exposure (main site is colon)
bull Clinical FIP found as early as 2 wk old to 18 months
and elderly gt 12 yr
bull From pyogranulomatous inflammation to clinical signs may be many months
เรามาถงจดนไดอยางไร
Objective Knowing FCoVs
Clinical relationship of FCoVs FECV and FIPV
Feline coronavirus classification flowchart
A Kipar and M L Meli Vet Pathol 201451505-526
Copyright copy by American College of Veterinary Pathologists
Feline coronavirus classification flowchart
A Kipar and M L Meli Vet Pathol 201451505-526
Copyright copy by American College of Veterinary Pathologists
CCoV FCoV TGEV
bull All group 1 Coronavirus are antigenically related
bull FCoV is divided into 2 serotypes bull FCoV 1
bull FCoV 2
bull FCoV 2 is antigenically similar to CCoV
( FCoV 2 is a recombinant of FCoV and CCoV)
bull BUT most field-strains are FCoV 1
Genetic relationships between the different feline and canine
coronaviruses genotypes (FCoV CCoV and TGEV)
From wwwgooglecom
FCoVs ndashwho are they
FCoV I
FCoV II
2 serotypes
FCoVs ndashwho are they
FCoV I
FCoV II
2 serotypes
2 biotypes pathotypes
FECV
FIPV
Enteric biotype Virulent biotype
FECVFIPV -serologicalmorphological undistinguishable
Prevalence of Feline Coronaviruses (FCoV)
Housed cats
bull 25-40 of cats infected with FCoV
Multi cat household colonies
bull 80-100 of cats infected with FCoV
In high prevalent area occurrence of FIP ~ 10
How FECV turn into FIPV
bull Two theories
ndash Internal mutation
ndash Circulating virulent avirulent viruses
bull FIPV and FECV strains can be serotpye I or II
Mutation when FECV turns into FIPV
Internal mutation theory
bull Genetic changes from FECV to FIPV in individual infected cat
bull Various types of mutation within 3c gene
bull 20 of kittens infected with FECV will produce an FIP mutant
Molecular Studies for diagnosis of FIP
bull Conflicting results
bull FCoV 1 (FIPV I) hellipvirulent bull FCoV II (FIPV II)hellipnon-virulent
Pathogenesis of FIP controversial
bull Immune-mediated vasculitis
bull Immune complex Type 3 hypersensitivity disease
Ag + Ab +compliments +C3
bull Pathological morphology
ndash Activation of monocytes
macrophages
ndash Monocyte-mediated viremia
ndash Granulomatous phleblitis periphlebitis
ndash VEGF ndash mediators increase vascular permeability
Endothelial cells show strongly MHCII antigen positive
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Activated macrophages
Morphologic Features and Development of Granulomatous vasculitis in FIP Kipar et al(2005)
Emigration of FCoV ndashinfected monocytes to vascular perivascular granulomatous infiltrates
with destruction of vascular basal laminar
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Leptomeningeal veins Agglomerate of TNF-α-positive monocytes attached to
venous endothelium Avidin-biotin-peroxidase complex method Papanicolaous hematoxylin counterstain Bar = 10 μm
Objective bullKnowing FCoVs
bullFCoVs in clinical diagnosis
Serology and Molecular diagnosis
Indirect FCoV antibody test Direct (viral load) FCoV RT-PCR
bull Blood
bull Feces
bull Effusion fluid
bull CSF
bull At present NO nucleoprotein sequences unique to pathogenic FCoV (ie not also present in nonpathogenic FCoV) have been identified
FCoV FECV FCoV where are they
Small intestinal enterocytes
Colon -rectum
Healthy shedders
Asymptomatic or mild diarrhea
After clearance from sm intestine FCoVs spread to infect colon and intermittently shedded off
If kittens infected before immune system fully mature levels of FECV replication will be very high
Reinfection may be from FCoV same strains or different strains
Pyogranulomatous inflammation
FIPV infected monocytes perivascular macrophages overproduce neutrophil survival factors Tumor necrosis factor- alpha (TNF ndashalpha) bull Matrix metalloproyeinase-9 bull GM-CSF bull G-CSF Neutrophil survival Development of granuloma lesions
Interpretation of FCoV antibody test
Viral shedding ~ 2 days (FCoV in epithelial cells)
Signs of FIP
bull As early as 2 wk old to 18 months
bull From pyogranulomatous inflammation to clinical signs may be months
From NC Pederson et al (2008) Feline enteric coronavirus infection
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To rule out FIP in sick cats bull effusive FIP
bull non- effusive FIP ( esp cats with GI signs)
bull To screen the FCoV excretors bull Cats in contact with known FCoV shedder
bull Cats in the household
bull New kitten or new cat bringing into the multi-cat household
bull Before receiving immunosuppressive treatment or stressful procedures
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To screen a breeding queen
bull To monitor FIP treatment q 8-12 wks
bull To screen blood donor cat
bull To screen prior to FeLV vaccination
Blood fluid Interpretation of FCoV antibody test
I false negative in sick FIP cat
II High titer (gt 11600) in normal cat (esp cat from multi-household) is not indicated FIP
III High titer in fluid high PPV
IV Generally not recommended in sick cat
FCoV antibody in CSF
bull Use of anti-coronavirus antibody testing of cerebrospinal fluid for diagnosis of feline infectious peritonitis involving the central nervous system in cats
bull J Am Vet Med Assoc January 2007230(2)199-205
bull Irene C Boettcher1 Tanja Steinberg Kaspar Matiasek Craig E Greene Katrin Hartmann Andrea Fischer
CSF IgG was detected only in strongly seropositive cats suggested that CSF anti-coronavirus IgG was derived from blood Measurement of
anti-coronavirus IgG in CSF was of equivocal clinical use
Test test test
FCoV RT-PCR test ( bloodeffusion fluidfeces)
Blood FCoV RT-PCR FECV Monocyte-associated viremia Not differentiate FIPV from pathotype
FCoV
Fecal FCoV RT-PC Recommend for house-cat management BUT single positive or negative tests are
meaningless as cats may shed intermittently or may be recently infected
Effusion fluid FCoV RT-PCR bull Generally recommended for fluid bull Positive result high PPV bull But 30 of effusions from cats
with FIP may be negative by RT-PCR
Why false negative 1 FIPV is cell-associated and likely confined to cells of perivascular granuloma (leaking out of pure plasma) 2 Inhibition of RT-PCR by interfering substances in fluid Therefore negative result doesnrsquot exclude FIP
Is FIP a contagious disease (cat-to-cat transmission)
Is FIP a contagious disease (cat-to-cat transmission)
Cats with FIP do not excrete pathogenic FIPV
FECV in enterocytes
Is FIP contagious
Cats with FIP do not appear to be very contagious to cats coming in contact with
Every FIPV isolated from a group outbreak of FIP does NOT genetically identical in its 3c gene mutation
However FIPV is found in the feces of most cats with FIP
Mutation when FECV turns into FIPV
Internal mutation theory bull Genetic changes from FECV
to FIPV
bull Various types of mutation within OPFs 3 and 7
bull 20 of kittens infected with FECV will produce an FIP mutant
Horizontal (cat-to cat) bull Transmission of FIPV
mutants
bull cats with FIP are shedding the same FIPV in their feces
J Gen Virol 2010 Feb91(Pt 2)415-20 doi 101099vir0016485-0 Epub 2009 Nov 4
Feline infectious peritonitis insights into feline coronavirus
pathobiogenesis and epidemiology based on genetic analysis of the viral
3c gene Chang HW1 de Groot RJ Egberink HF Rottier PJ
helliphellipMost cats with FIP had no detectable intestinal feline coronaviruses (FCoVs) and
had seemingly cleared the primary FECV infection In those with detectable intestinal
FCoV the virus always had an intact 3c and seemed to have been acquired by FECV
superinfection Apparently 3c-inactivated viruses replicate not at all--or only poorly--in the
gut explaining the rare incidence of FIP outbreaks
FIP transmission
FIP transmission
bull Vet Res 2013 Jul 174457 doi 1011861297-9716-44-57
bull An outbreak of feline infectious peritonitis in a Taiwanese shelter epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus
bull Wang YT1 Su BL Hsieh LE Chueh LL
bull Abstract
bull helliphellipSequence analysis revealed that the type II FIPV detected from fecal samples body
effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death Taken together our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment
FCoV field strain in FIP cat
Genomic RNA sequence of feline coronavirus strain FCoV C1Je Charlotte Dye BVMampS PhD CertSAM MRCVS
Stuart G Siddell BSc(Hons) PhD
bull This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV) Viral RNAs isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP) derived 100 nucleotide identity
Feline Coronavirus serotypes I and II were reported in natural infection
bull Feline coronavirus serotypes 1 and 2 seroprevalence and association with disease in Switzerland
bull Clin Diagn Lab Immunol October 200512(10)1209-15 bull Maya Kummrow1 Marina L Meli Michael Haessig Enikoe Goenczi Amy Poland Niels C
Pedersen Regina Hofmann-Lehmann Hans Lutz
bull Comparison of serologic techniques for the detection of antibodies against feline coronaviruses
bull J Vet Diagn Invest January 200820(1)45-50 bull Annamaria Pratelli1
bull Prevalence of Korean cats with natural feline coronavirus infections bull Virol J January 20118(0)455 bull Dong-Jun An1 Hye-Young Jeoung Wooseog Jeong Jee Yong Park Myoung-Heon Lee Bong
Kyun Park bull 1National Veterinary Research and Quarantine Service Anyang Kyunggi-do430-824 Korea
bull Moreshellip
Take home message Knowing ME knowing YOU
My team my world
Thank you
เรามาถงจดนไดอยางไร
Objective Knowing FCoVs
Clinical relationship of FCoVs FECV and FIPV
Feline coronavirus classification flowchart
A Kipar and M L Meli Vet Pathol 201451505-526
Copyright copy by American College of Veterinary Pathologists
Feline coronavirus classification flowchart
A Kipar and M L Meli Vet Pathol 201451505-526
Copyright copy by American College of Veterinary Pathologists
CCoV FCoV TGEV
bull All group 1 Coronavirus are antigenically related
bull FCoV is divided into 2 serotypes bull FCoV 1
bull FCoV 2
bull FCoV 2 is antigenically similar to CCoV
( FCoV 2 is a recombinant of FCoV and CCoV)
bull BUT most field-strains are FCoV 1
Genetic relationships between the different feline and canine
coronaviruses genotypes (FCoV CCoV and TGEV)
From wwwgooglecom
FCoVs ndashwho are they
FCoV I
FCoV II
2 serotypes
FCoVs ndashwho are they
FCoV I
FCoV II
2 serotypes
2 biotypes pathotypes
FECV
FIPV
Enteric biotype Virulent biotype
FECVFIPV -serologicalmorphological undistinguishable
Prevalence of Feline Coronaviruses (FCoV)
Housed cats
bull 25-40 of cats infected with FCoV
Multi cat household colonies
bull 80-100 of cats infected with FCoV
In high prevalent area occurrence of FIP ~ 10
How FECV turn into FIPV
bull Two theories
ndash Internal mutation
ndash Circulating virulent avirulent viruses
bull FIPV and FECV strains can be serotpye I or II
Mutation when FECV turns into FIPV
Internal mutation theory
bull Genetic changes from FECV to FIPV in individual infected cat
bull Various types of mutation within 3c gene
bull 20 of kittens infected with FECV will produce an FIP mutant
Molecular Studies for diagnosis of FIP
bull Conflicting results
bull FCoV 1 (FIPV I) hellipvirulent bull FCoV II (FIPV II)hellipnon-virulent
Pathogenesis of FIP controversial
bull Immune-mediated vasculitis
bull Immune complex Type 3 hypersensitivity disease
Ag + Ab +compliments +C3
bull Pathological morphology
ndash Activation of monocytes
macrophages
ndash Monocyte-mediated viremia
ndash Granulomatous phleblitis periphlebitis
ndash VEGF ndash mediators increase vascular permeability
Endothelial cells show strongly MHCII antigen positive
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Activated macrophages
Morphologic Features and Development of Granulomatous vasculitis in FIP Kipar et al(2005)
Emigration of FCoV ndashinfected monocytes to vascular perivascular granulomatous infiltrates
with destruction of vascular basal laminar
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Leptomeningeal veins Agglomerate of TNF-α-positive monocytes attached to
venous endothelium Avidin-biotin-peroxidase complex method Papanicolaous hematoxylin counterstain Bar = 10 μm
Objective bullKnowing FCoVs
bullFCoVs in clinical diagnosis
Serology and Molecular diagnosis
Indirect FCoV antibody test Direct (viral load) FCoV RT-PCR
bull Blood
bull Feces
bull Effusion fluid
bull CSF
bull At present NO nucleoprotein sequences unique to pathogenic FCoV (ie not also present in nonpathogenic FCoV) have been identified
FCoV FECV FCoV where are they
Small intestinal enterocytes
Colon -rectum
Healthy shedders
Asymptomatic or mild diarrhea
After clearance from sm intestine FCoVs spread to infect colon and intermittently shedded off
If kittens infected before immune system fully mature levels of FECV replication will be very high
Reinfection may be from FCoV same strains or different strains
Pyogranulomatous inflammation
FIPV infected monocytes perivascular macrophages overproduce neutrophil survival factors Tumor necrosis factor- alpha (TNF ndashalpha) bull Matrix metalloproyeinase-9 bull GM-CSF bull G-CSF Neutrophil survival Development of granuloma lesions
Interpretation of FCoV antibody test
Viral shedding ~ 2 days (FCoV in epithelial cells)
Signs of FIP
bull As early as 2 wk old to 18 months
bull From pyogranulomatous inflammation to clinical signs may be months
From NC Pederson et al (2008) Feline enteric coronavirus infection
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To rule out FIP in sick cats bull effusive FIP
bull non- effusive FIP ( esp cats with GI signs)
bull To screen the FCoV excretors bull Cats in contact with known FCoV shedder
bull Cats in the household
bull New kitten or new cat bringing into the multi-cat household
bull Before receiving immunosuppressive treatment or stressful procedures
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To screen a breeding queen
bull To monitor FIP treatment q 8-12 wks
bull To screen blood donor cat
bull To screen prior to FeLV vaccination
Blood fluid Interpretation of FCoV antibody test
I false negative in sick FIP cat
II High titer (gt 11600) in normal cat (esp cat from multi-household) is not indicated FIP
III High titer in fluid high PPV
IV Generally not recommended in sick cat
FCoV antibody in CSF
bull Use of anti-coronavirus antibody testing of cerebrospinal fluid for diagnosis of feline infectious peritonitis involving the central nervous system in cats
bull J Am Vet Med Assoc January 2007230(2)199-205
bull Irene C Boettcher1 Tanja Steinberg Kaspar Matiasek Craig E Greene Katrin Hartmann Andrea Fischer
CSF IgG was detected only in strongly seropositive cats suggested that CSF anti-coronavirus IgG was derived from blood Measurement of
anti-coronavirus IgG in CSF was of equivocal clinical use
Test test test
FCoV RT-PCR test ( bloodeffusion fluidfeces)
Blood FCoV RT-PCR FECV Monocyte-associated viremia Not differentiate FIPV from pathotype
FCoV
Fecal FCoV RT-PC Recommend for house-cat management BUT single positive or negative tests are
meaningless as cats may shed intermittently or may be recently infected
Effusion fluid FCoV RT-PCR bull Generally recommended for fluid bull Positive result high PPV bull But 30 of effusions from cats
with FIP may be negative by RT-PCR
Why false negative 1 FIPV is cell-associated and likely confined to cells of perivascular granuloma (leaking out of pure plasma) 2 Inhibition of RT-PCR by interfering substances in fluid Therefore negative result doesnrsquot exclude FIP
Is FIP a contagious disease (cat-to-cat transmission)
Is FIP a contagious disease (cat-to-cat transmission)
Cats with FIP do not excrete pathogenic FIPV
FECV in enterocytes
Is FIP contagious
Cats with FIP do not appear to be very contagious to cats coming in contact with
Every FIPV isolated from a group outbreak of FIP does NOT genetically identical in its 3c gene mutation
However FIPV is found in the feces of most cats with FIP
Mutation when FECV turns into FIPV
Internal mutation theory bull Genetic changes from FECV
to FIPV
bull Various types of mutation within OPFs 3 and 7
bull 20 of kittens infected with FECV will produce an FIP mutant
Horizontal (cat-to cat) bull Transmission of FIPV
mutants
bull cats with FIP are shedding the same FIPV in their feces
J Gen Virol 2010 Feb91(Pt 2)415-20 doi 101099vir0016485-0 Epub 2009 Nov 4
Feline infectious peritonitis insights into feline coronavirus
pathobiogenesis and epidemiology based on genetic analysis of the viral
3c gene Chang HW1 de Groot RJ Egberink HF Rottier PJ
helliphellipMost cats with FIP had no detectable intestinal feline coronaviruses (FCoVs) and
had seemingly cleared the primary FECV infection In those with detectable intestinal
FCoV the virus always had an intact 3c and seemed to have been acquired by FECV
superinfection Apparently 3c-inactivated viruses replicate not at all--or only poorly--in the
gut explaining the rare incidence of FIP outbreaks
FIP transmission
FIP transmission
bull Vet Res 2013 Jul 174457 doi 1011861297-9716-44-57
bull An outbreak of feline infectious peritonitis in a Taiwanese shelter epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus
bull Wang YT1 Su BL Hsieh LE Chueh LL
bull Abstract
bull helliphellipSequence analysis revealed that the type II FIPV detected from fecal samples body
effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death Taken together our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment
FCoV field strain in FIP cat
Genomic RNA sequence of feline coronavirus strain FCoV C1Je Charlotte Dye BVMampS PhD CertSAM MRCVS
Stuart G Siddell BSc(Hons) PhD
bull This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV) Viral RNAs isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP) derived 100 nucleotide identity
Feline Coronavirus serotypes I and II were reported in natural infection
bull Feline coronavirus serotypes 1 and 2 seroprevalence and association with disease in Switzerland
bull Clin Diagn Lab Immunol October 200512(10)1209-15 bull Maya Kummrow1 Marina L Meli Michael Haessig Enikoe Goenczi Amy Poland Niels C
Pedersen Regina Hofmann-Lehmann Hans Lutz
bull Comparison of serologic techniques for the detection of antibodies against feline coronaviruses
bull J Vet Diagn Invest January 200820(1)45-50 bull Annamaria Pratelli1
bull Prevalence of Korean cats with natural feline coronavirus infections bull Virol J January 20118(0)455 bull Dong-Jun An1 Hye-Young Jeoung Wooseog Jeong Jee Yong Park Myoung-Heon Lee Bong
Kyun Park bull 1National Veterinary Research and Quarantine Service Anyang Kyunggi-do430-824 Korea
bull Moreshellip
Take home message Knowing ME knowing YOU
My team my world
Thank you
Objective Knowing FCoVs
Clinical relationship of FCoVs FECV and FIPV
Feline coronavirus classification flowchart
A Kipar and M L Meli Vet Pathol 201451505-526
Copyright copy by American College of Veterinary Pathologists
Feline coronavirus classification flowchart
A Kipar and M L Meli Vet Pathol 201451505-526
Copyright copy by American College of Veterinary Pathologists
CCoV FCoV TGEV
bull All group 1 Coronavirus are antigenically related
bull FCoV is divided into 2 serotypes bull FCoV 1
bull FCoV 2
bull FCoV 2 is antigenically similar to CCoV
( FCoV 2 is a recombinant of FCoV and CCoV)
bull BUT most field-strains are FCoV 1
Genetic relationships between the different feline and canine
coronaviruses genotypes (FCoV CCoV and TGEV)
From wwwgooglecom
FCoVs ndashwho are they
FCoV I
FCoV II
2 serotypes
FCoVs ndashwho are they
FCoV I
FCoV II
2 serotypes
2 biotypes pathotypes
FECV
FIPV
Enteric biotype Virulent biotype
FECVFIPV -serologicalmorphological undistinguishable
Prevalence of Feline Coronaviruses (FCoV)
Housed cats
bull 25-40 of cats infected with FCoV
Multi cat household colonies
bull 80-100 of cats infected with FCoV
In high prevalent area occurrence of FIP ~ 10
How FECV turn into FIPV
bull Two theories
ndash Internal mutation
ndash Circulating virulent avirulent viruses
bull FIPV and FECV strains can be serotpye I or II
Mutation when FECV turns into FIPV
Internal mutation theory
bull Genetic changes from FECV to FIPV in individual infected cat
bull Various types of mutation within 3c gene
bull 20 of kittens infected with FECV will produce an FIP mutant
Molecular Studies for diagnosis of FIP
bull Conflicting results
bull FCoV 1 (FIPV I) hellipvirulent bull FCoV II (FIPV II)hellipnon-virulent
Pathogenesis of FIP controversial
bull Immune-mediated vasculitis
bull Immune complex Type 3 hypersensitivity disease
Ag + Ab +compliments +C3
bull Pathological morphology
ndash Activation of monocytes
macrophages
ndash Monocyte-mediated viremia
ndash Granulomatous phleblitis periphlebitis
ndash VEGF ndash mediators increase vascular permeability
Endothelial cells show strongly MHCII antigen positive
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Activated macrophages
Morphologic Features and Development of Granulomatous vasculitis in FIP Kipar et al(2005)
Emigration of FCoV ndashinfected monocytes to vascular perivascular granulomatous infiltrates
with destruction of vascular basal laminar
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Leptomeningeal veins Agglomerate of TNF-α-positive monocytes attached to
venous endothelium Avidin-biotin-peroxidase complex method Papanicolaous hematoxylin counterstain Bar = 10 μm
Objective bullKnowing FCoVs
bullFCoVs in clinical diagnosis
Serology and Molecular diagnosis
Indirect FCoV antibody test Direct (viral load) FCoV RT-PCR
bull Blood
bull Feces
bull Effusion fluid
bull CSF
bull At present NO nucleoprotein sequences unique to pathogenic FCoV (ie not also present in nonpathogenic FCoV) have been identified
FCoV FECV FCoV where are they
Small intestinal enterocytes
Colon -rectum
Healthy shedders
Asymptomatic or mild diarrhea
After clearance from sm intestine FCoVs spread to infect colon and intermittently shedded off
If kittens infected before immune system fully mature levels of FECV replication will be very high
Reinfection may be from FCoV same strains or different strains
Pyogranulomatous inflammation
FIPV infected monocytes perivascular macrophages overproduce neutrophil survival factors Tumor necrosis factor- alpha (TNF ndashalpha) bull Matrix metalloproyeinase-9 bull GM-CSF bull G-CSF Neutrophil survival Development of granuloma lesions
Interpretation of FCoV antibody test
Viral shedding ~ 2 days (FCoV in epithelial cells)
Signs of FIP
bull As early as 2 wk old to 18 months
bull From pyogranulomatous inflammation to clinical signs may be months
From NC Pederson et al (2008) Feline enteric coronavirus infection
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To rule out FIP in sick cats bull effusive FIP
bull non- effusive FIP ( esp cats with GI signs)
bull To screen the FCoV excretors bull Cats in contact with known FCoV shedder
bull Cats in the household
bull New kitten or new cat bringing into the multi-cat household
bull Before receiving immunosuppressive treatment or stressful procedures
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To screen a breeding queen
bull To monitor FIP treatment q 8-12 wks
bull To screen blood donor cat
bull To screen prior to FeLV vaccination
Blood fluid Interpretation of FCoV antibody test
I false negative in sick FIP cat
II High titer (gt 11600) in normal cat (esp cat from multi-household) is not indicated FIP
III High titer in fluid high PPV
IV Generally not recommended in sick cat
FCoV antibody in CSF
bull Use of anti-coronavirus antibody testing of cerebrospinal fluid for diagnosis of feline infectious peritonitis involving the central nervous system in cats
bull J Am Vet Med Assoc January 2007230(2)199-205
bull Irene C Boettcher1 Tanja Steinberg Kaspar Matiasek Craig E Greene Katrin Hartmann Andrea Fischer
CSF IgG was detected only in strongly seropositive cats suggested that CSF anti-coronavirus IgG was derived from blood Measurement of
anti-coronavirus IgG in CSF was of equivocal clinical use
Test test test
FCoV RT-PCR test ( bloodeffusion fluidfeces)
Blood FCoV RT-PCR FECV Monocyte-associated viremia Not differentiate FIPV from pathotype
FCoV
Fecal FCoV RT-PC Recommend for house-cat management BUT single positive or negative tests are
meaningless as cats may shed intermittently or may be recently infected
Effusion fluid FCoV RT-PCR bull Generally recommended for fluid bull Positive result high PPV bull But 30 of effusions from cats
with FIP may be negative by RT-PCR
Why false negative 1 FIPV is cell-associated and likely confined to cells of perivascular granuloma (leaking out of pure plasma) 2 Inhibition of RT-PCR by interfering substances in fluid Therefore negative result doesnrsquot exclude FIP
Is FIP a contagious disease (cat-to-cat transmission)
Is FIP a contagious disease (cat-to-cat transmission)
Cats with FIP do not excrete pathogenic FIPV
FECV in enterocytes
Is FIP contagious
Cats with FIP do not appear to be very contagious to cats coming in contact with
Every FIPV isolated from a group outbreak of FIP does NOT genetically identical in its 3c gene mutation
However FIPV is found in the feces of most cats with FIP
Mutation when FECV turns into FIPV
Internal mutation theory bull Genetic changes from FECV
to FIPV
bull Various types of mutation within OPFs 3 and 7
bull 20 of kittens infected with FECV will produce an FIP mutant
Horizontal (cat-to cat) bull Transmission of FIPV
mutants
bull cats with FIP are shedding the same FIPV in their feces
J Gen Virol 2010 Feb91(Pt 2)415-20 doi 101099vir0016485-0 Epub 2009 Nov 4
Feline infectious peritonitis insights into feline coronavirus
pathobiogenesis and epidemiology based on genetic analysis of the viral
3c gene Chang HW1 de Groot RJ Egberink HF Rottier PJ
helliphellipMost cats with FIP had no detectable intestinal feline coronaviruses (FCoVs) and
had seemingly cleared the primary FECV infection In those with detectable intestinal
FCoV the virus always had an intact 3c and seemed to have been acquired by FECV
superinfection Apparently 3c-inactivated viruses replicate not at all--or only poorly--in the
gut explaining the rare incidence of FIP outbreaks
FIP transmission
FIP transmission
bull Vet Res 2013 Jul 174457 doi 1011861297-9716-44-57
bull An outbreak of feline infectious peritonitis in a Taiwanese shelter epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus
bull Wang YT1 Su BL Hsieh LE Chueh LL
bull Abstract
bull helliphellipSequence analysis revealed that the type II FIPV detected from fecal samples body
effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death Taken together our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment
FCoV field strain in FIP cat
Genomic RNA sequence of feline coronavirus strain FCoV C1Je Charlotte Dye BVMampS PhD CertSAM MRCVS
Stuart G Siddell BSc(Hons) PhD
bull This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV) Viral RNAs isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP) derived 100 nucleotide identity
Feline Coronavirus serotypes I and II were reported in natural infection
bull Feline coronavirus serotypes 1 and 2 seroprevalence and association with disease in Switzerland
bull Clin Diagn Lab Immunol October 200512(10)1209-15 bull Maya Kummrow1 Marina L Meli Michael Haessig Enikoe Goenczi Amy Poland Niels C
Pedersen Regina Hofmann-Lehmann Hans Lutz
bull Comparison of serologic techniques for the detection of antibodies against feline coronaviruses
bull J Vet Diagn Invest January 200820(1)45-50 bull Annamaria Pratelli1
bull Prevalence of Korean cats with natural feline coronavirus infections bull Virol J January 20118(0)455 bull Dong-Jun An1 Hye-Young Jeoung Wooseog Jeong Jee Yong Park Myoung-Heon Lee Bong
Kyun Park bull 1National Veterinary Research and Quarantine Service Anyang Kyunggi-do430-824 Korea
bull Moreshellip
Take home message Knowing ME knowing YOU
My team my world
Thank you
Clinical relationship of FCoVs FECV and FIPV
Feline coronavirus classification flowchart
A Kipar and M L Meli Vet Pathol 201451505-526
Copyright copy by American College of Veterinary Pathologists
Feline coronavirus classification flowchart
A Kipar and M L Meli Vet Pathol 201451505-526
Copyright copy by American College of Veterinary Pathologists
CCoV FCoV TGEV
bull All group 1 Coronavirus are antigenically related
bull FCoV is divided into 2 serotypes bull FCoV 1
bull FCoV 2
bull FCoV 2 is antigenically similar to CCoV
( FCoV 2 is a recombinant of FCoV and CCoV)
bull BUT most field-strains are FCoV 1
Genetic relationships between the different feline and canine
coronaviruses genotypes (FCoV CCoV and TGEV)
From wwwgooglecom
FCoVs ndashwho are they
FCoV I
FCoV II
2 serotypes
FCoVs ndashwho are they
FCoV I
FCoV II
2 serotypes
2 biotypes pathotypes
FECV
FIPV
Enteric biotype Virulent biotype
FECVFIPV -serologicalmorphological undistinguishable
Prevalence of Feline Coronaviruses (FCoV)
Housed cats
bull 25-40 of cats infected with FCoV
Multi cat household colonies
bull 80-100 of cats infected with FCoV
In high prevalent area occurrence of FIP ~ 10
How FECV turn into FIPV
bull Two theories
ndash Internal mutation
ndash Circulating virulent avirulent viruses
bull FIPV and FECV strains can be serotpye I or II
Mutation when FECV turns into FIPV
Internal mutation theory
bull Genetic changes from FECV to FIPV in individual infected cat
bull Various types of mutation within 3c gene
bull 20 of kittens infected with FECV will produce an FIP mutant
Molecular Studies for diagnosis of FIP
bull Conflicting results
bull FCoV 1 (FIPV I) hellipvirulent bull FCoV II (FIPV II)hellipnon-virulent
Pathogenesis of FIP controversial
bull Immune-mediated vasculitis
bull Immune complex Type 3 hypersensitivity disease
Ag + Ab +compliments +C3
bull Pathological morphology
ndash Activation of monocytes
macrophages
ndash Monocyte-mediated viremia
ndash Granulomatous phleblitis periphlebitis
ndash VEGF ndash mediators increase vascular permeability
Endothelial cells show strongly MHCII antigen positive
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Activated macrophages
Morphologic Features and Development of Granulomatous vasculitis in FIP Kipar et al(2005)
Emigration of FCoV ndashinfected monocytes to vascular perivascular granulomatous infiltrates
with destruction of vascular basal laminar
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Leptomeningeal veins Agglomerate of TNF-α-positive monocytes attached to
venous endothelium Avidin-biotin-peroxidase complex method Papanicolaous hematoxylin counterstain Bar = 10 μm
Objective bullKnowing FCoVs
bullFCoVs in clinical diagnosis
Serology and Molecular diagnosis
Indirect FCoV antibody test Direct (viral load) FCoV RT-PCR
bull Blood
bull Feces
bull Effusion fluid
bull CSF
bull At present NO nucleoprotein sequences unique to pathogenic FCoV (ie not also present in nonpathogenic FCoV) have been identified
FCoV FECV FCoV where are they
Small intestinal enterocytes
Colon -rectum
Healthy shedders
Asymptomatic or mild diarrhea
After clearance from sm intestine FCoVs spread to infect colon and intermittently shedded off
If kittens infected before immune system fully mature levels of FECV replication will be very high
Reinfection may be from FCoV same strains or different strains
Pyogranulomatous inflammation
FIPV infected monocytes perivascular macrophages overproduce neutrophil survival factors Tumor necrosis factor- alpha (TNF ndashalpha) bull Matrix metalloproyeinase-9 bull GM-CSF bull G-CSF Neutrophil survival Development of granuloma lesions
Interpretation of FCoV antibody test
Viral shedding ~ 2 days (FCoV in epithelial cells)
Signs of FIP
bull As early as 2 wk old to 18 months
bull From pyogranulomatous inflammation to clinical signs may be months
From NC Pederson et al (2008) Feline enteric coronavirus infection
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To rule out FIP in sick cats bull effusive FIP
bull non- effusive FIP ( esp cats with GI signs)
bull To screen the FCoV excretors bull Cats in contact with known FCoV shedder
bull Cats in the household
bull New kitten or new cat bringing into the multi-cat household
bull Before receiving immunosuppressive treatment or stressful procedures
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To screen a breeding queen
bull To monitor FIP treatment q 8-12 wks
bull To screen blood donor cat
bull To screen prior to FeLV vaccination
Blood fluid Interpretation of FCoV antibody test
I false negative in sick FIP cat
II High titer (gt 11600) in normal cat (esp cat from multi-household) is not indicated FIP
III High titer in fluid high PPV
IV Generally not recommended in sick cat
FCoV antibody in CSF
bull Use of anti-coronavirus antibody testing of cerebrospinal fluid for diagnosis of feline infectious peritonitis involving the central nervous system in cats
bull J Am Vet Med Assoc January 2007230(2)199-205
bull Irene C Boettcher1 Tanja Steinberg Kaspar Matiasek Craig E Greene Katrin Hartmann Andrea Fischer
CSF IgG was detected only in strongly seropositive cats suggested that CSF anti-coronavirus IgG was derived from blood Measurement of
anti-coronavirus IgG in CSF was of equivocal clinical use
Test test test
FCoV RT-PCR test ( bloodeffusion fluidfeces)
Blood FCoV RT-PCR FECV Monocyte-associated viremia Not differentiate FIPV from pathotype
FCoV
Fecal FCoV RT-PC Recommend for house-cat management BUT single positive or negative tests are
meaningless as cats may shed intermittently or may be recently infected
Effusion fluid FCoV RT-PCR bull Generally recommended for fluid bull Positive result high PPV bull But 30 of effusions from cats
with FIP may be negative by RT-PCR
Why false negative 1 FIPV is cell-associated and likely confined to cells of perivascular granuloma (leaking out of pure plasma) 2 Inhibition of RT-PCR by interfering substances in fluid Therefore negative result doesnrsquot exclude FIP
Is FIP a contagious disease (cat-to-cat transmission)
Is FIP a contagious disease (cat-to-cat transmission)
Cats with FIP do not excrete pathogenic FIPV
FECV in enterocytes
Is FIP contagious
Cats with FIP do not appear to be very contagious to cats coming in contact with
Every FIPV isolated from a group outbreak of FIP does NOT genetically identical in its 3c gene mutation
However FIPV is found in the feces of most cats with FIP
Mutation when FECV turns into FIPV
Internal mutation theory bull Genetic changes from FECV
to FIPV
bull Various types of mutation within OPFs 3 and 7
bull 20 of kittens infected with FECV will produce an FIP mutant
Horizontal (cat-to cat) bull Transmission of FIPV
mutants
bull cats with FIP are shedding the same FIPV in their feces
J Gen Virol 2010 Feb91(Pt 2)415-20 doi 101099vir0016485-0 Epub 2009 Nov 4
Feline infectious peritonitis insights into feline coronavirus
pathobiogenesis and epidemiology based on genetic analysis of the viral
3c gene Chang HW1 de Groot RJ Egberink HF Rottier PJ
helliphellipMost cats with FIP had no detectable intestinal feline coronaviruses (FCoVs) and
had seemingly cleared the primary FECV infection In those with detectable intestinal
FCoV the virus always had an intact 3c and seemed to have been acquired by FECV
superinfection Apparently 3c-inactivated viruses replicate not at all--or only poorly--in the
gut explaining the rare incidence of FIP outbreaks
FIP transmission
FIP transmission
bull Vet Res 2013 Jul 174457 doi 1011861297-9716-44-57
bull An outbreak of feline infectious peritonitis in a Taiwanese shelter epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus
bull Wang YT1 Su BL Hsieh LE Chueh LL
bull Abstract
bull helliphellipSequence analysis revealed that the type II FIPV detected from fecal samples body
effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death Taken together our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment
FCoV field strain in FIP cat
Genomic RNA sequence of feline coronavirus strain FCoV C1Je Charlotte Dye BVMampS PhD CertSAM MRCVS
Stuart G Siddell BSc(Hons) PhD
bull This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV) Viral RNAs isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP) derived 100 nucleotide identity
Feline Coronavirus serotypes I and II were reported in natural infection
bull Feline coronavirus serotypes 1 and 2 seroprevalence and association with disease in Switzerland
bull Clin Diagn Lab Immunol October 200512(10)1209-15 bull Maya Kummrow1 Marina L Meli Michael Haessig Enikoe Goenczi Amy Poland Niels C
Pedersen Regina Hofmann-Lehmann Hans Lutz
bull Comparison of serologic techniques for the detection of antibodies against feline coronaviruses
bull J Vet Diagn Invest January 200820(1)45-50 bull Annamaria Pratelli1
bull Prevalence of Korean cats with natural feline coronavirus infections bull Virol J January 20118(0)455 bull Dong-Jun An1 Hye-Young Jeoung Wooseog Jeong Jee Yong Park Myoung-Heon Lee Bong
Kyun Park bull 1National Veterinary Research and Quarantine Service Anyang Kyunggi-do430-824 Korea
bull Moreshellip
Take home message Knowing ME knowing YOU
My team my world
Thank you
Feline coronavirus classification flowchart
A Kipar and M L Meli Vet Pathol 201451505-526
Copyright copy by American College of Veterinary Pathologists
Feline coronavirus classification flowchart
A Kipar and M L Meli Vet Pathol 201451505-526
Copyright copy by American College of Veterinary Pathologists
CCoV FCoV TGEV
bull All group 1 Coronavirus are antigenically related
bull FCoV is divided into 2 serotypes bull FCoV 1
bull FCoV 2
bull FCoV 2 is antigenically similar to CCoV
( FCoV 2 is a recombinant of FCoV and CCoV)
bull BUT most field-strains are FCoV 1
Genetic relationships between the different feline and canine
coronaviruses genotypes (FCoV CCoV and TGEV)
From wwwgooglecom
FCoVs ndashwho are they
FCoV I
FCoV II
2 serotypes
FCoVs ndashwho are they
FCoV I
FCoV II
2 serotypes
2 biotypes pathotypes
FECV
FIPV
Enteric biotype Virulent biotype
FECVFIPV -serologicalmorphological undistinguishable
Prevalence of Feline Coronaviruses (FCoV)
Housed cats
bull 25-40 of cats infected with FCoV
Multi cat household colonies
bull 80-100 of cats infected with FCoV
In high prevalent area occurrence of FIP ~ 10
How FECV turn into FIPV
bull Two theories
ndash Internal mutation
ndash Circulating virulent avirulent viruses
bull FIPV and FECV strains can be serotpye I or II
Mutation when FECV turns into FIPV
Internal mutation theory
bull Genetic changes from FECV to FIPV in individual infected cat
bull Various types of mutation within 3c gene
bull 20 of kittens infected with FECV will produce an FIP mutant
Molecular Studies for diagnosis of FIP
bull Conflicting results
bull FCoV 1 (FIPV I) hellipvirulent bull FCoV II (FIPV II)hellipnon-virulent
Pathogenesis of FIP controversial
bull Immune-mediated vasculitis
bull Immune complex Type 3 hypersensitivity disease
Ag + Ab +compliments +C3
bull Pathological morphology
ndash Activation of monocytes
macrophages
ndash Monocyte-mediated viremia
ndash Granulomatous phleblitis periphlebitis
ndash VEGF ndash mediators increase vascular permeability
Endothelial cells show strongly MHCII antigen positive
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Activated macrophages
Morphologic Features and Development of Granulomatous vasculitis in FIP Kipar et al(2005)
Emigration of FCoV ndashinfected monocytes to vascular perivascular granulomatous infiltrates
with destruction of vascular basal laminar
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Leptomeningeal veins Agglomerate of TNF-α-positive monocytes attached to
venous endothelium Avidin-biotin-peroxidase complex method Papanicolaous hematoxylin counterstain Bar = 10 μm
Objective bullKnowing FCoVs
bullFCoVs in clinical diagnosis
Serology and Molecular diagnosis
Indirect FCoV antibody test Direct (viral load) FCoV RT-PCR
bull Blood
bull Feces
bull Effusion fluid
bull CSF
bull At present NO nucleoprotein sequences unique to pathogenic FCoV (ie not also present in nonpathogenic FCoV) have been identified
FCoV FECV FCoV where are they
Small intestinal enterocytes
Colon -rectum
Healthy shedders
Asymptomatic or mild diarrhea
After clearance from sm intestine FCoVs spread to infect colon and intermittently shedded off
If kittens infected before immune system fully mature levels of FECV replication will be very high
Reinfection may be from FCoV same strains or different strains
Pyogranulomatous inflammation
FIPV infected monocytes perivascular macrophages overproduce neutrophil survival factors Tumor necrosis factor- alpha (TNF ndashalpha) bull Matrix metalloproyeinase-9 bull GM-CSF bull G-CSF Neutrophil survival Development of granuloma lesions
Interpretation of FCoV antibody test
Viral shedding ~ 2 days (FCoV in epithelial cells)
Signs of FIP
bull As early as 2 wk old to 18 months
bull From pyogranulomatous inflammation to clinical signs may be months
From NC Pederson et al (2008) Feline enteric coronavirus infection
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To rule out FIP in sick cats bull effusive FIP
bull non- effusive FIP ( esp cats with GI signs)
bull To screen the FCoV excretors bull Cats in contact with known FCoV shedder
bull Cats in the household
bull New kitten or new cat bringing into the multi-cat household
bull Before receiving immunosuppressive treatment or stressful procedures
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To screen a breeding queen
bull To monitor FIP treatment q 8-12 wks
bull To screen blood donor cat
bull To screen prior to FeLV vaccination
Blood fluid Interpretation of FCoV antibody test
I false negative in sick FIP cat
II High titer (gt 11600) in normal cat (esp cat from multi-household) is not indicated FIP
III High titer in fluid high PPV
IV Generally not recommended in sick cat
FCoV antibody in CSF
bull Use of anti-coronavirus antibody testing of cerebrospinal fluid for diagnosis of feline infectious peritonitis involving the central nervous system in cats
bull J Am Vet Med Assoc January 2007230(2)199-205
bull Irene C Boettcher1 Tanja Steinberg Kaspar Matiasek Craig E Greene Katrin Hartmann Andrea Fischer
CSF IgG was detected only in strongly seropositive cats suggested that CSF anti-coronavirus IgG was derived from blood Measurement of
anti-coronavirus IgG in CSF was of equivocal clinical use
Test test test
FCoV RT-PCR test ( bloodeffusion fluidfeces)
Blood FCoV RT-PCR FECV Monocyte-associated viremia Not differentiate FIPV from pathotype
FCoV
Fecal FCoV RT-PC Recommend for house-cat management BUT single positive or negative tests are
meaningless as cats may shed intermittently or may be recently infected
Effusion fluid FCoV RT-PCR bull Generally recommended for fluid bull Positive result high PPV bull But 30 of effusions from cats
with FIP may be negative by RT-PCR
Why false negative 1 FIPV is cell-associated and likely confined to cells of perivascular granuloma (leaking out of pure plasma) 2 Inhibition of RT-PCR by interfering substances in fluid Therefore negative result doesnrsquot exclude FIP
Is FIP a contagious disease (cat-to-cat transmission)
Is FIP a contagious disease (cat-to-cat transmission)
Cats with FIP do not excrete pathogenic FIPV
FECV in enterocytes
Is FIP contagious
Cats with FIP do not appear to be very contagious to cats coming in contact with
Every FIPV isolated from a group outbreak of FIP does NOT genetically identical in its 3c gene mutation
However FIPV is found in the feces of most cats with FIP
Mutation when FECV turns into FIPV
Internal mutation theory bull Genetic changes from FECV
to FIPV
bull Various types of mutation within OPFs 3 and 7
bull 20 of kittens infected with FECV will produce an FIP mutant
Horizontal (cat-to cat) bull Transmission of FIPV
mutants
bull cats with FIP are shedding the same FIPV in their feces
J Gen Virol 2010 Feb91(Pt 2)415-20 doi 101099vir0016485-0 Epub 2009 Nov 4
Feline infectious peritonitis insights into feline coronavirus
pathobiogenesis and epidemiology based on genetic analysis of the viral
3c gene Chang HW1 de Groot RJ Egberink HF Rottier PJ
helliphellipMost cats with FIP had no detectable intestinal feline coronaviruses (FCoVs) and
had seemingly cleared the primary FECV infection In those with detectable intestinal
FCoV the virus always had an intact 3c and seemed to have been acquired by FECV
superinfection Apparently 3c-inactivated viruses replicate not at all--or only poorly--in the
gut explaining the rare incidence of FIP outbreaks
FIP transmission
FIP transmission
bull Vet Res 2013 Jul 174457 doi 1011861297-9716-44-57
bull An outbreak of feline infectious peritonitis in a Taiwanese shelter epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus
bull Wang YT1 Su BL Hsieh LE Chueh LL
bull Abstract
bull helliphellipSequence analysis revealed that the type II FIPV detected from fecal samples body
effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death Taken together our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment
FCoV field strain in FIP cat
Genomic RNA sequence of feline coronavirus strain FCoV C1Je Charlotte Dye BVMampS PhD CertSAM MRCVS
Stuart G Siddell BSc(Hons) PhD
bull This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV) Viral RNAs isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP) derived 100 nucleotide identity
Feline Coronavirus serotypes I and II were reported in natural infection
bull Feline coronavirus serotypes 1 and 2 seroprevalence and association with disease in Switzerland
bull Clin Diagn Lab Immunol October 200512(10)1209-15 bull Maya Kummrow1 Marina L Meli Michael Haessig Enikoe Goenczi Amy Poland Niels C
Pedersen Regina Hofmann-Lehmann Hans Lutz
bull Comparison of serologic techniques for the detection of antibodies against feline coronaviruses
bull J Vet Diagn Invest January 200820(1)45-50 bull Annamaria Pratelli1
bull Prevalence of Korean cats with natural feline coronavirus infections bull Virol J January 20118(0)455 bull Dong-Jun An1 Hye-Young Jeoung Wooseog Jeong Jee Yong Park Myoung-Heon Lee Bong
Kyun Park bull 1National Veterinary Research and Quarantine Service Anyang Kyunggi-do430-824 Korea
bull Moreshellip
Take home message Knowing ME knowing YOU
My team my world
Thank you
Feline coronavirus classification flowchart
A Kipar and M L Meli Vet Pathol 201451505-526
Copyright copy by American College of Veterinary Pathologists
CCoV FCoV TGEV
bull All group 1 Coronavirus are antigenically related
bull FCoV is divided into 2 serotypes bull FCoV 1
bull FCoV 2
bull FCoV 2 is antigenically similar to CCoV
( FCoV 2 is a recombinant of FCoV and CCoV)
bull BUT most field-strains are FCoV 1
Genetic relationships between the different feline and canine
coronaviruses genotypes (FCoV CCoV and TGEV)
From wwwgooglecom
FCoVs ndashwho are they
FCoV I
FCoV II
2 serotypes
FCoVs ndashwho are they
FCoV I
FCoV II
2 serotypes
2 biotypes pathotypes
FECV
FIPV
Enteric biotype Virulent biotype
FECVFIPV -serologicalmorphological undistinguishable
Prevalence of Feline Coronaviruses (FCoV)
Housed cats
bull 25-40 of cats infected with FCoV
Multi cat household colonies
bull 80-100 of cats infected with FCoV
In high prevalent area occurrence of FIP ~ 10
How FECV turn into FIPV
bull Two theories
ndash Internal mutation
ndash Circulating virulent avirulent viruses
bull FIPV and FECV strains can be serotpye I or II
Mutation when FECV turns into FIPV
Internal mutation theory
bull Genetic changes from FECV to FIPV in individual infected cat
bull Various types of mutation within 3c gene
bull 20 of kittens infected with FECV will produce an FIP mutant
Molecular Studies for diagnosis of FIP
bull Conflicting results
bull FCoV 1 (FIPV I) hellipvirulent bull FCoV II (FIPV II)hellipnon-virulent
Pathogenesis of FIP controversial
bull Immune-mediated vasculitis
bull Immune complex Type 3 hypersensitivity disease
Ag + Ab +compliments +C3
bull Pathological morphology
ndash Activation of monocytes
macrophages
ndash Monocyte-mediated viremia
ndash Granulomatous phleblitis periphlebitis
ndash VEGF ndash mediators increase vascular permeability
Endothelial cells show strongly MHCII antigen positive
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Activated macrophages
Morphologic Features and Development of Granulomatous vasculitis in FIP Kipar et al(2005)
Emigration of FCoV ndashinfected monocytes to vascular perivascular granulomatous infiltrates
with destruction of vascular basal laminar
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Leptomeningeal veins Agglomerate of TNF-α-positive monocytes attached to
venous endothelium Avidin-biotin-peroxidase complex method Papanicolaous hematoxylin counterstain Bar = 10 μm
Objective bullKnowing FCoVs
bullFCoVs in clinical diagnosis
Serology and Molecular diagnosis
Indirect FCoV antibody test Direct (viral load) FCoV RT-PCR
bull Blood
bull Feces
bull Effusion fluid
bull CSF
bull At present NO nucleoprotein sequences unique to pathogenic FCoV (ie not also present in nonpathogenic FCoV) have been identified
FCoV FECV FCoV where are they
Small intestinal enterocytes
Colon -rectum
Healthy shedders
Asymptomatic or mild diarrhea
After clearance from sm intestine FCoVs spread to infect colon and intermittently shedded off
If kittens infected before immune system fully mature levels of FECV replication will be very high
Reinfection may be from FCoV same strains or different strains
Pyogranulomatous inflammation
FIPV infected monocytes perivascular macrophages overproduce neutrophil survival factors Tumor necrosis factor- alpha (TNF ndashalpha) bull Matrix metalloproyeinase-9 bull GM-CSF bull G-CSF Neutrophil survival Development of granuloma lesions
Interpretation of FCoV antibody test
Viral shedding ~ 2 days (FCoV in epithelial cells)
Signs of FIP
bull As early as 2 wk old to 18 months
bull From pyogranulomatous inflammation to clinical signs may be months
From NC Pederson et al (2008) Feline enteric coronavirus infection
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To rule out FIP in sick cats bull effusive FIP
bull non- effusive FIP ( esp cats with GI signs)
bull To screen the FCoV excretors bull Cats in contact with known FCoV shedder
bull Cats in the household
bull New kitten or new cat bringing into the multi-cat household
bull Before receiving immunosuppressive treatment or stressful procedures
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To screen a breeding queen
bull To monitor FIP treatment q 8-12 wks
bull To screen blood donor cat
bull To screen prior to FeLV vaccination
Blood fluid Interpretation of FCoV antibody test
I false negative in sick FIP cat
II High titer (gt 11600) in normal cat (esp cat from multi-household) is not indicated FIP
III High titer in fluid high PPV
IV Generally not recommended in sick cat
FCoV antibody in CSF
bull Use of anti-coronavirus antibody testing of cerebrospinal fluid for diagnosis of feline infectious peritonitis involving the central nervous system in cats
bull J Am Vet Med Assoc January 2007230(2)199-205
bull Irene C Boettcher1 Tanja Steinberg Kaspar Matiasek Craig E Greene Katrin Hartmann Andrea Fischer
CSF IgG was detected only in strongly seropositive cats suggested that CSF anti-coronavirus IgG was derived from blood Measurement of
anti-coronavirus IgG in CSF was of equivocal clinical use
Test test test
FCoV RT-PCR test ( bloodeffusion fluidfeces)
Blood FCoV RT-PCR FECV Monocyte-associated viremia Not differentiate FIPV from pathotype
FCoV
Fecal FCoV RT-PC Recommend for house-cat management BUT single positive or negative tests are
meaningless as cats may shed intermittently or may be recently infected
Effusion fluid FCoV RT-PCR bull Generally recommended for fluid bull Positive result high PPV bull But 30 of effusions from cats
with FIP may be negative by RT-PCR
Why false negative 1 FIPV is cell-associated and likely confined to cells of perivascular granuloma (leaking out of pure plasma) 2 Inhibition of RT-PCR by interfering substances in fluid Therefore negative result doesnrsquot exclude FIP
Is FIP a contagious disease (cat-to-cat transmission)
Is FIP a contagious disease (cat-to-cat transmission)
Cats with FIP do not excrete pathogenic FIPV
FECV in enterocytes
Is FIP contagious
Cats with FIP do not appear to be very contagious to cats coming in contact with
Every FIPV isolated from a group outbreak of FIP does NOT genetically identical in its 3c gene mutation
However FIPV is found in the feces of most cats with FIP
Mutation when FECV turns into FIPV
Internal mutation theory bull Genetic changes from FECV
to FIPV
bull Various types of mutation within OPFs 3 and 7
bull 20 of kittens infected with FECV will produce an FIP mutant
Horizontal (cat-to cat) bull Transmission of FIPV
mutants
bull cats with FIP are shedding the same FIPV in their feces
J Gen Virol 2010 Feb91(Pt 2)415-20 doi 101099vir0016485-0 Epub 2009 Nov 4
Feline infectious peritonitis insights into feline coronavirus
pathobiogenesis and epidemiology based on genetic analysis of the viral
3c gene Chang HW1 de Groot RJ Egberink HF Rottier PJ
helliphellipMost cats with FIP had no detectable intestinal feline coronaviruses (FCoVs) and
had seemingly cleared the primary FECV infection In those with detectable intestinal
FCoV the virus always had an intact 3c and seemed to have been acquired by FECV
superinfection Apparently 3c-inactivated viruses replicate not at all--or only poorly--in the
gut explaining the rare incidence of FIP outbreaks
FIP transmission
FIP transmission
bull Vet Res 2013 Jul 174457 doi 1011861297-9716-44-57
bull An outbreak of feline infectious peritonitis in a Taiwanese shelter epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus
bull Wang YT1 Su BL Hsieh LE Chueh LL
bull Abstract
bull helliphellipSequence analysis revealed that the type II FIPV detected from fecal samples body
effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death Taken together our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment
FCoV field strain in FIP cat
Genomic RNA sequence of feline coronavirus strain FCoV C1Je Charlotte Dye BVMampS PhD CertSAM MRCVS
Stuart G Siddell BSc(Hons) PhD
bull This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV) Viral RNAs isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP) derived 100 nucleotide identity
Feline Coronavirus serotypes I and II were reported in natural infection
bull Feline coronavirus serotypes 1 and 2 seroprevalence and association with disease in Switzerland
bull Clin Diagn Lab Immunol October 200512(10)1209-15 bull Maya Kummrow1 Marina L Meli Michael Haessig Enikoe Goenczi Amy Poland Niels C
Pedersen Regina Hofmann-Lehmann Hans Lutz
bull Comparison of serologic techniques for the detection of antibodies against feline coronaviruses
bull J Vet Diagn Invest January 200820(1)45-50 bull Annamaria Pratelli1
bull Prevalence of Korean cats with natural feline coronavirus infections bull Virol J January 20118(0)455 bull Dong-Jun An1 Hye-Young Jeoung Wooseog Jeong Jee Yong Park Myoung-Heon Lee Bong
Kyun Park bull 1National Veterinary Research and Quarantine Service Anyang Kyunggi-do430-824 Korea
bull Moreshellip
Take home message Knowing ME knowing YOU
My team my world
Thank you
CCoV FCoV TGEV
bull All group 1 Coronavirus are antigenically related
bull FCoV is divided into 2 serotypes bull FCoV 1
bull FCoV 2
bull FCoV 2 is antigenically similar to CCoV
( FCoV 2 is a recombinant of FCoV and CCoV)
bull BUT most field-strains are FCoV 1
Genetic relationships between the different feline and canine
coronaviruses genotypes (FCoV CCoV and TGEV)
From wwwgooglecom
FCoVs ndashwho are they
FCoV I
FCoV II
2 serotypes
FCoVs ndashwho are they
FCoV I
FCoV II
2 serotypes
2 biotypes pathotypes
FECV
FIPV
Enteric biotype Virulent biotype
FECVFIPV -serologicalmorphological undistinguishable
Prevalence of Feline Coronaviruses (FCoV)
Housed cats
bull 25-40 of cats infected with FCoV
Multi cat household colonies
bull 80-100 of cats infected with FCoV
In high prevalent area occurrence of FIP ~ 10
How FECV turn into FIPV
bull Two theories
ndash Internal mutation
ndash Circulating virulent avirulent viruses
bull FIPV and FECV strains can be serotpye I or II
Mutation when FECV turns into FIPV
Internal mutation theory
bull Genetic changes from FECV to FIPV in individual infected cat
bull Various types of mutation within 3c gene
bull 20 of kittens infected with FECV will produce an FIP mutant
Molecular Studies for diagnosis of FIP
bull Conflicting results
bull FCoV 1 (FIPV I) hellipvirulent bull FCoV II (FIPV II)hellipnon-virulent
Pathogenesis of FIP controversial
bull Immune-mediated vasculitis
bull Immune complex Type 3 hypersensitivity disease
Ag + Ab +compliments +C3
bull Pathological morphology
ndash Activation of monocytes
macrophages
ndash Monocyte-mediated viremia
ndash Granulomatous phleblitis periphlebitis
ndash VEGF ndash mediators increase vascular permeability
Endothelial cells show strongly MHCII antigen positive
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Activated macrophages
Morphologic Features and Development of Granulomatous vasculitis in FIP Kipar et al(2005)
Emigration of FCoV ndashinfected monocytes to vascular perivascular granulomatous infiltrates
with destruction of vascular basal laminar
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Leptomeningeal veins Agglomerate of TNF-α-positive monocytes attached to
venous endothelium Avidin-biotin-peroxidase complex method Papanicolaous hematoxylin counterstain Bar = 10 μm
Objective bullKnowing FCoVs
bullFCoVs in clinical diagnosis
Serology and Molecular diagnosis
Indirect FCoV antibody test Direct (viral load) FCoV RT-PCR
bull Blood
bull Feces
bull Effusion fluid
bull CSF
bull At present NO nucleoprotein sequences unique to pathogenic FCoV (ie not also present in nonpathogenic FCoV) have been identified
FCoV FECV FCoV where are they
Small intestinal enterocytes
Colon -rectum
Healthy shedders
Asymptomatic or mild diarrhea
After clearance from sm intestine FCoVs spread to infect colon and intermittently shedded off
If kittens infected before immune system fully mature levels of FECV replication will be very high
Reinfection may be from FCoV same strains or different strains
Pyogranulomatous inflammation
FIPV infected monocytes perivascular macrophages overproduce neutrophil survival factors Tumor necrosis factor- alpha (TNF ndashalpha) bull Matrix metalloproyeinase-9 bull GM-CSF bull G-CSF Neutrophil survival Development of granuloma lesions
Interpretation of FCoV antibody test
Viral shedding ~ 2 days (FCoV in epithelial cells)
Signs of FIP
bull As early as 2 wk old to 18 months
bull From pyogranulomatous inflammation to clinical signs may be months
From NC Pederson et al (2008) Feline enteric coronavirus infection
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To rule out FIP in sick cats bull effusive FIP
bull non- effusive FIP ( esp cats with GI signs)
bull To screen the FCoV excretors bull Cats in contact with known FCoV shedder
bull Cats in the household
bull New kitten or new cat bringing into the multi-cat household
bull Before receiving immunosuppressive treatment or stressful procedures
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To screen a breeding queen
bull To monitor FIP treatment q 8-12 wks
bull To screen blood donor cat
bull To screen prior to FeLV vaccination
Blood fluid Interpretation of FCoV antibody test
I false negative in sick FIP cat
II High titer (gt 11600) in normal cat (esp cat from multi-household) is not indicated FIP
III High titer in fluid high PPV
IV Generally not recommended in sick cat
FCoV antibody in CSF
bull Use of anti-coronavirus antibody testing of cerebrospinal fluid for diagnosis of feline infectious peritonitis involving the central nervous system in cats
bull J Am Vet Med Assoc January 2007230(2)199-205
bull Irene C Boettcher1 Tanja Steinberg Kaspar Matiasek Craig E Greene Katrin Hartmann Andrea Fischer
CSF IgG was detected only in strongly seropositive cats suggested that CSF anti-coronavirus IgG was derived from blood Measurement of
anti-coronavirus IgG in CSF was of equivocal clinical use
Test test test
FCoV RT-PCR test ( bloodeffusion fluidfeces)
Blood FCoV RT-PCR FECV Monocyte-associated viremia Not differentiate FIPV from pathotype
FCoV
Fecal FCoV RT-PC Recommend for house-cat management BUT single positive or negative tests are
meaningless as cats may shed intermittently or may be recently infected
Effusion fluid FCoV RT-PCR bull Generally recommended for fluid bull Positive result high PPV bull But 30 of effusions from cats
with FIP may be negative by RT-PCR
Why false negative 1 FIPV is cell-associated and likely confined to cells of perivascular granuloma (leaking out of pure plasma) 2 Inhibition of RT-PCR by interfering substances in fluid Therefore negative result doesnrsquot exclude FIP
Is FIP a contagious disease (cat-to-cat transmission)
Is FIP a contagious disease (cat-to-cat transmission)
Cats with FIP do not excrete pathogenic FIPV
FECV in enterocytes
Is FIP contagious
Cats with FIP do not appear to be very contagious to cats coming in contact with
Every FIPV isolated from a group outbreak of FIP does NOT genetically identical in its 3c gene mutation
However FIPV is found in the feces of most cats with FIP
Mutation when FECV turns into FIPV
Internal mutation theory bull Genetic changes from FECV
to FIPV
bull Various types of mutation within OPFs 3 and 7
bull 20 of kittens infected with FECV will produce an FIP mutant
Horizontal (cat-to cat) bull Transmission of FIPV
mutants
bull cats with FIP are shedding the same FIPV in their feces
J Gen Virol 2010 Feb91(Pt 2)415-20 doi 101099vir0016485-0 Epub 2009 Nov 4
Feline infectious peritonitis insights into feline coronavirus
pathobiogenesis and epidemiology based on genetic analysis of the viral
3c gene Chang HW1 de Groot RJ Egberink HF Rottier PJ
helliphellipMost cats with FIP had no detectable intestinal feline coronaviruses (FCoVs) and
had seemingly cleared the primary FECV infection In those with detectable intestinal
FCoV the virus always had an intact 3c and seemed to have been acquired by FECV
superinfection Apparently 3c-inactivated viruses replicate not at all--or only poorly--in the
gut explaining the rare incidence of FIP outbreaks
FIP transmission
FIP transmission
bull Vet Res 2013 Jul 174457 doi 1011861297-9716-44-57
bull An outbreak of feline infectious peritonitis in a Taiwanese shelter epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus
bull Wang YT1 Su BL Hsieh LE Chueh LL
bull Abstract
bull helliphellipSequence analysis revealed that the type II FIPV detected from fecal samples body
effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death Taken together our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment
FCoV field strain in FIP cat
Genomic RNA sequence of feline coronavirus strain FCoV C1Je Charlotte Dye BVMampS PhD CertSAM MRCVS
Stuart G Siddell BSc(Hons) PhD
bull This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV) Viral RNAs isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP) derived 100 nucleotide identity
Feline Coronavirus serotypes I and II were reported in natural infection
bull Feline coronavirus serotypes 1 and 2 seroprevalence and association with disease in Switzerland
bull Clin Diagn Lab Immunol October 200512(10)1209-15 bull Maya Kummrow1 Marina L Meli Michael Haessig Enikoe Goenczi Amy Poland Niels C
Pedersen Regina Hofmann-Lehmann Hans Lutz
bull Comparison of serologic techniques for the detection of antibodies against feline coronaviruses
bull J Vet Diagn Invest January 200820(1)45-50 bull Annamaria Pratelli1
bull Prevalence of Korean cats with natural feline coronavirus infections bull Virol J January 20118(0)455 bull Dong-Jun An1 Hye-Young Jeoung Wooseog Jeong Jee Yong Park Myoung-Heon Lee Bong
Kyun Park bull 1National Veterinary Research and Quarantine Service Anyang Kyunggi-do430-824 Korea
bull Moreshellip
Take home message Knowing ME knowing YOU
My team my world
Thank you
Genetic relationships between the different feline and canine
coronaviruses genotypes (FCoV CCoV and TGEV)
From wwwgooglecom
FCoVs ndashwho are they
FCoV I
FCoV II
2 serotypes
FCoVs ndashwho are they
FCoV I
FCoV II
2 serotypes
2 biotypes pathotypes
FECV
FIPV
Enteric biotype Virulent biotype
FECVFIPV -serologicalmorphological undistinguishable
Prevalence of Feline Coronaviruses (FCoV)
Housed cats
bull 25-40 of cats infected with FCoV
Multi cat household colonies
bull 80-100 of cats infected with FCoV
In high prevalent area occurrence of FIP ~ 10
How FECV turn into FIPV
bull Two theories
ndash Internal mutation
ndash Circulating virulent avirulent viruses
bull FIPV and FECV strains can be serotpye I or II
Mutation when FECV turns into FIPV
Internal mutation theory
bull Genetic changes from FECV to FIPV in individual infected cat
bull Various types of mutation within 3c gene
bull 20 of kittens infected with FECV will produce an FIP mutant
Molecular Studies for diagnosis of FIP
bull Conflicting results
bull FCoV 1 (FIPV I) hellipvirulent bull FCoV II (FIPV II)hellipnon-virulent
Pathogenesis of FIP controversial
bull Immune-mediated vasculitis
bull Immune complex Type 3 hypersensitivity disease
Ag + Ab +compliments +C3
bull Pathological morphology
ndash Activation of monocytes
macrophages
ndash Monocyte-mediated viremia
ndash Granulomatous phleblitis periphlebitis
ndash VEGF ndash mediators increase vascular permeability
Endothelial cells show strongly MHCII antigen positive
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Activated macrophages
Morphologic Features and Development of Granulomatous vasculitis in FIP Kipar et al(2005)
Emigration of FCoV ndashinfected monocytes to vascular perivascular granulomatous infiltrates
with destruction of vascular basal laminar
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Leptomeningeal veins Agglomerate of TNF-α-positive monocytes attached to
venous endothelium Avidin-biotin-peroxidase complex method Papanicolaous hematoxylin counterstain Bar = 10 μm
Objective bullKnowing FCoVs
bullFCoVs in clinical diagnosis
Serology and Molecular diagnosis
Indirect FCoV antibody test Direct (viral load) FCoV RT-PCR
bull Blood
bull Feces
bull Effusion fluid
bull CSF
bull At present NO nucleoprotein sequences unique to pathogenic FCoV (ie not also present in nonpathogenic FCoV) have been identified
FCoV FECV FCoV where are they
Small intestinal enterocytes
Colon -rectum
Healthy shedders
Asymptomatic or mild diarrhea
After clearance from sm intestine FCoVs spread to infect colon and intermittently shedded off
If kittens infected before immune system fully mature levels of FECV replication will be very high
Reinfection may be from FCoV same strains or different strains
Pyogranulomatous inflammation
FIPV infected monocytes perivascular macrophages overproduce neutrophil survival factors Tumor necrosis factor- alpha (TNF ndashalpha) bull Matrix metalloproyeinase-9 bull GM-CSF bull G-CSF Neutrophil survival Development of granuloma lesions
Interpretation of FCoV antibody test
Viral shedding ~ 2 days (FCoV in epithelial cells)
Signs of FIP
bull As early as 2 wk old to 18 months
bull From pyogranulomatous inflammation to clinical signs may be months
From NC Pederson et al (2008) Feline enteric coronavirus infection
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To rule out FIP in sick cats bull effusive FIP
bull non- effusive FIP ( esp cats with GI signs)
bull To screen the FCoV excretors bull Cats in contact with known FCoV shedder
bull Cats in the household
bull New kitten or new cat bringing into the multi-cat household
bull Before receiving immunosuppressive treatment or stressful procedures
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To screen a breeding queen
bull To monitor FIP treatment q 8-12 wks
bull To screen blood donor cat
bull To screen prior to FeLV vaccination
Blood fluid Interpretation of FCoV antibody test
I false negative in sick FIP cat
II High titer (gt 11600) in normal cat (esp cat from multi-household) is not indicated FIP
III High titer in fluid high PPV
IV Generally not recommended in sick cat
FCoV antibody in CSF
bull Use of anti-coronavirus antibody testing of cerebrospinal fluid for diagnosis of feline infectious peritonitis involving the central nervous system in cats
bull J Am Vet Med Assoc January 2007230(2)199-205
bull Irene C Boettcher1 Tanja Steinberg Kaspar Matiasek Craig E Greene Katrin Hartmann Andrea Fischer
CSF IgG was detected only in strongly seropositive cats suggested that CSF anti-coronavirus IgG was derived from blood Measurement of
anti-coronavirus IgG in CSF was of equivocal clinical use
Test test test
FCoV RT-PCR test ( bloodeffusion fluidfeces)
Blood FCoV RT-PCR FECV Monocyte-associated viremia Not differentiate FIPV from pathotype
FCoV
Fecal FCoV RT-PC Recommend for house-cat management BUT single positive or negative tests are
meaningless as cats may shed intermittently or may be recently infected
Effusion fluid FCoV RT-PCR bull Generally recommended for fluid bull Positive result high PPV bull But 30 of effusions from cats
with FIP may be negative by RT-PCR
Why false negative 1 FIPV is cell-associated and likely confined to cells of perivascular granuloma (leaking out of pure plasma) 2 Inhibition of RT-PCR by interfering substances in fluid Therefore negative result doesnrsquot exclude FIP
Is FIP a contagious disease (cat-to-cat transmission)
Is FIP a contagious disease (cat-to-cat transmission)
Cats with FIP do not excrete pathogenic FIPV
FECV in enterocytes
Is FIP contagious
Cats with FIP do not appear to be very contagious to cats coming in contact with
Every FIPV isolated from a group outbreak of FIP does NOT genetically identical in its 3c gene mutation
However FIPV is found in the feces of most cats with FIP
Mutation when FECV turns into FIPV
Internal mutation theory bull Genetic changes from FECV
to FIPV
bull Various types of mutation within OPFs 3 and 7
bull 20 of kittens infected with FECV will produce an FIP mutant
Horizontal (cat-to cat) bull Transmission of FIPV
mutants
bull cats with FIP are shedding the same FIPV in their feces
J Gen Virol 2010 Feb91(Pt 2)415-20 doi 101099vir0016485-0 Epub 2009 Nov 4
Feline infectious peritonitis insights into feline coronavirus
pathobiogenesis and epidemiology based on genetic analysis of the viral
3c gene Chang HW1 de Groot RJ Egberink HF Rottier PJ
helliphellipMost cats with FIP had no detectable intestinal feline coronaviruses (FCoVs) and
had seemingly cleared the primary FECV infection In those with detectable intestinal
FCoV the virus always had an intact 3c and seemed to have been acquired by FECV
superinfection Apparently 3c-inactivated viruses replicate not at all--or only poorly--in the
gut explaining the rare incidence of FIP outbreaks
FIP transmission
FIP transmission
bull Vet Res 2013 Jul 174457 doi 1011861297-9716-44-57
bull An outbreak of feline infectious peritonitis in a Taiwanese shelter epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus
bull Wang YT1 Su BL Hsieh LE Chueh LL
bull Abstract
bull helliphellipSequence analysis revealed that the type II FIPV detected from fecal samples body
effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death Taken together our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment
FCoV field strain in FIP cat
Genomic RNA sequence of feline coronavirus strain FCoV C1Je Charlotte Dye BVMampS PhD CertSAM MRCVS
Stuart G Siddell BSc(Hons) PhD
bull This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV) Viral RNAs isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP) derived 100 nucleotide identity
Feline Coronavirus serotypes I and II were reported in natural infection
bull Feline coronavirus serotypes 1 and 2 seroprevalence and association with disease in Switzerland
bull Clin Diagn Lab Immunol October 200512(10)1209-15 bull Maya Kummrow1 Marina L Meli Michael Haessig Enikoe Goenczi Amy Poland Niels C
Pedersen Regina Hofmann-Lehmann Hans Lutz
bull Comparison of serologic techniques for the detection of antibodies against feline coronaviruses
bull J Vet Diagn Invest January 200820(1)45-50 bull Annamaria Pratelli1
bull Prevalence of Korean cats with natural feline coronavirus infections bull Virol J January 20118(0)455 bull Dong-Jun An1 Hye-Young Jeoung Wooseog Jeong Jee Yong Park Myoung-Heon Lee Bong
Kyun Park bull 1National Veterinary Research and Quarantine Service Anyang Kyunggi-do430-824 Korea
bull Moreshellip
Take home message Knowing ME knowing YOU
My team my world
Thank you
FCoVs ndashwho are they
FCoV I
FCoV II
2 serotypes
FCoVs ndashwho are they
FCoV I
FCoV II
2 serotypes
2 biotypes pathotypes
FECV
FIPV
Enteric biotype Virulent biotype
FECVFIPV -serologicalmorphological undistinguishable
Prevalence of Feline Coronaviruses (FCoV)
Housed cats
bull 25-40 of cats infected with FCoV
Multi cat household colonies
bull 80-100 of cats infected with FCoV
In high prevalent area occurrence of FIP ~ 10
How FECV turn into FIPV
bull Two theories
ndash Internal mutation
ndash Circulating virulent avirulent viruses
bull FIPV and FECV strains can be serotpye I or II
Mutation when FECV turns into FIPV
Internal mutation theory
bull Genetic changes from FECV to FIPV in individual infected cat
bull Various types of mutation within 3c gene
bull 20 of kittens infected with FECV will produce an FIP mutant
Molecular Studies for diagnosis of FIP
bull Conflicting results
bull FCoV 1 (FIPV I) hellipvirulent bull FCoV II (FIPV II)hellipnon-virulent
Pathogenesis of FIP controversial
bull Immune-mediated vasculitis
bull Immune complex Type 3 hypersensitivity disease
Ag + Ab +compliments +C3
bull Pathological morphology
ndash Activation of monocytes
macrophages
ndash Monocyte-mediated viremia
ndash Granulomatous phleblitis periphlebitis
ndash VEGF ndash mediators increase vascular permeability
Endothelial cells show strongly MHCII antigen positive
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Activated macrophages
Morphologic Features and Development of Granulomatous vasculitis in FIP Kipar et al(2005)
Emigration of FCoV ndashinfected monocytes to vascular perivascular granulomatous infiltrates
with destruction of vascular basal laminar
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Leptomeningeal veins Agglomerate of TNF-α-positive monocytes attached to
venous endothelium Avidin-biotin-peroxidase complex method Papanicolaous hematoxylin counterstain Bar = 10 μm
Objective bullKnowing FCoVs
bullFCoVs in clinical diagnosis
Serology and Molecular diagnosis
Indirect FCoV antibody test Direct (viral load) FCoV RT-PCR
bull Blood
bull Feces
bull Effusion fluid
bull CSF
bull At present NO nucleoprotein sequences unique to pathogenic FCoV (ie not also present in nonpathogenic FCoV) have been identified
FCoV FECV FCoV where are they
Small intestinal enterocytes
Colon -rectum
Healthy shedders
Asymptomatic or mild diarrhea
After clearance from sm intestine FCoVs spread to infect colon and intermittently shedded off
If kittens infected before immune system fully mature levels of FECV replication will be very high
Reinfection may be from FCoV same strains or different strains
Pyogranulomatous inflammation
FIPV infected monocytes perivascular macrophages overproduce neutrophil survival factors Tumor necrosis factor- alpha (TNF ndashalpha) bull Matrix metalloproyeinase-9 bull GM-CSF bull G-CSF Neutrophil survival Development of granuloma lesions
Interpretation of FCoV antibody test
Viral shedding ~ 2 days (FCoV in epithelial cells)
Signs of FIP
bull As early as 2 wk old to 18 months
bull From pyogranulomatous inflammation to clinical signs may be months
From NC Pederson et al (2008) Feline enteric coronavirus infection
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To rule out FIP in sick cats bull effusive FIP
bull non- effusive FIP ( esp cats with GI signs)
bull To screen the FCoV excretors bull Cats in contact with known FCoV shedder
bull Cats in the household
bull New kitten or new cat bringing into the multi-cat household
bull Before receiving immunosuppressive treatment or stressful procedures
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To screen a breeding queen
bull To monitor FIP treatment q 8-12 wks
bull To screen blood donor cat
bull To screen prior to FeLV vaccination
Blood fluid Interpretation of FCoV antibody test
I false negative in sick FIP cat
II High titer (gt 11600) in normal cat (esp cat from multi-household) is not indicated FIP
III High titer in fluid high PPV
IV Generally not recommended in sick cat
FCoV antibody in CSF
bull Use of anti-coronavirus antibody testing of cerebrospinal fluid for diagnosis of feline infectious peritonitis involving the central nervous system in cats
bull J Am Vet Med Assoc January 2007230(2)199-205
bull Irene C Boettcher1 Tanja Steinberg Kaspar Matiasek Craig E Greene Katrin Hartmann Andrea Fischer
CSF IgG was detected only in strongly seropositive cats suggested that CSF anti-coronavirus IgG was derived from blood Measurement of
anti-coronavirus IgG in CSF was of equivocal clinical use
Test test test
FCoV RT-PCR test ( bloodeffusion fluidfeces)
Blood FCoV RT-PCR FECV Monocyte-associated viremia Not differentiate FIPV from pathotype
FCoV
Fecal FCoV RT-PC Recommend for house-cat management BUT single positive or negative tests are
meaningless as cats may shed intermittently or may be recently infected
Effusion fluid FCoV RT-PCR bull Generally recommended for fluid bull Positive result high PPV bull But 30 of effusions from cats
with FIP may be negative by RT-PCR
Why false negative 1 FIPV is cell-associated and likely confined to cells of perivascular granuloma (leaking out of pure plasma) 2 Inhibition of RT-PCR by interfering substances in fluid Therefore negative result doesnrsquot exclude FIP
Is FIP a contagious disease (cat-to-cat transmission)
Is FIP a contagious disease (cat-to-cat transmission)
Cats with FIP do not excrete pathogenic FIPV
FECV in enterocytes
Is FIP contagious
Cats with FIP do not appear to be very contagious to cats coming in contact with
Every FIPV isolated from a group outbreak of FIP does NOT genetically identical in its 3c gene mutation
However FIPV is found in the feces of most cats with FIP
Mutation when FECV turns into FIPV
Internal mutation theory bull Genetic changes from FECV
to FIPV
bull Various types of mutation within OPFs 3 and 7
bull 20 of kittens infected with FECV will produce an FIP mutant
Horizontal (cat-to cat) bull Transmission of FIPV
mutants
bull cats with FIP are shedding the same FIPV in their feces
J Gen Virol 2010 Feb91(Pt 2)415-20 doi 101099vir0016485-0 Epub 2009 Nov 4
Feline infectious peritonitis insights into feline coronavirus
pathobiogenesis and epidemiology based on genetic analysis of the viral
3c gene Chang HW1 de Groot RJ Egberink HF Rottier PJ
helliphellipMost cats with FIP had no detectable intestinal feline coronaviruses (FCoVs) and
had seemingly cleared the primary FECV infection In those with detectable intestinal
FCoV the virus always had an intact 3c and seemed to have been acquired by FECV
superinfection Apparently 3c-inactivated viruses replicate not at all--or only poorly--in the
gut explaining the rare incidence of FIP outbreaks
FIP transmission
FIP transmission
bull Vet Res 2013 Jul 174457 doi 1011861297-9716-44-57
bull An outbreak of feline infectious peritonitis in a Taiwanese shelter epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus
bull Wang YT1 Su BL Hsieh LE Chueh LL
bull Abstract
bull helliphellipSequence analysis revealed that the type II FIPV detected from fecal samples body
effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death Taken together our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment
FCoV field strain in FIP cat
Genomic RNA sequence of feline coronavirus strain FCoV C1Je Charlotte Dye BVMampS PhD CertSAM MRCVS
Stuart G Siddell BSc(Hons) PhD
bull This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV) Viral RNAs isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP) derived 100 nucleotide identity
Feline Coronavirus serotypes I and II were reported in natural infection
bull Feline coronavirus serotypes 1 and 2 seroprevalence and association with disease in Switzerland
bull Clin Diagn Lab Immunol October 200512(10)1209-15 bull Maya Kummrow1 Marina L Meli Michael Haessig Enikoe Goenczi Amy Poland Niels C
Pedersen Regina Hofmann-Lehmann Hans Lutz
bull Comparison of serologic techniques for the detection of antibodies against feline coronaviruses
bull J Vet Diagn Invest January 200820(1)45-50 bull Annamaria Pratelli1
bull Prevalence of Korean cats with natural feline coronavirus infections bull Virol J January 20118(0)455 bull Dong-Jun An1 Hye-Young Jeoung Wooseog Jeong Jee Yong Park Myoung-Heon Lee Bong
Kyun Park bull 1National Veterinary Research and Quarantine Service Anyang Kyunggi-do430-824 Korea
bull Moreshellip
Take home message Knowing ME knowing YOU
My team my world
Thank you
FCoVs ndashwho are they
FCoV I
FCoV II
2 serotypes
2 biotypes pathotypes
FECV
FIPV
Enteric biotype Virulent biotype
FECVFIPV -serologicalmorphological undistinguishable
Prevalence of Feline Coronaviruses (FCoV)
Housed cats
bull 25-40 of cats infected with FCoV
Multi cat household colonies
bull 80-100 of cats infected with FCoV
In high prevalent area occurrence of FIP ~ 10
How FECV turn into FIPV
bull Two theories
ndash Internal mutation
ndash Circulating virulent avirulent viruses
bull FIPV and FECV strains can be serotpye I or II
Mutation when FECV turns into FIPV
Internal mutation theory
bull Genetic changes from FECV to FIPV in individual infected cat
bull Various types of mutation within 3c gene
bull 20 of kittens infected with FECV will produce an FIP mutant
Molecular Studies for diagnosis of FIP
bull Conflicting results
bull FCoV 1 (FIPV I) hellipvirulent bull FCoV II (FIPV II)hellipnon-virulent
Pathogenesis of FIP controversial
bull Immune-mediated vasculitis
bull Immune complex Type 3 hypersensitivity disease
Ag + Ab +compliments +C3
bull Pathological morphology
ndash Activation of monocytes
macrophages
ndash Monocyte-mediated viremia
ndash Granulomatous phleblitis periphlebitis
ndash VEGF ndash mediators increase vascular permeability
Endothelial cells show strongly MHCII antigen positive
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Activated macrophages
Morphologic Features and Development of Granulomatous vasculitis in FIP Kipar et al(2005)
Emigration of FCoV ndashinfected monocytes to vascular perivascular granulomatous infiltrates
with destruction of vascular basal laminar
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Leptomeningeal veins Agglomerate of TNF-α-positive monocytes attached to
venous endothelium Avidin-biotin-peroxidase complex method Papanicolaous hematoxylin counterstain Bar = 10 μm
Objective bullKnowing FCoVs
bullFCoVs in clinical diagnosis
Serology and Molecular diagnosis
Indirect FCoV antibody test Direct (viral load) FCoV RT-PCR
bull Blood
bull Feces
bull Effusion fluid
bull CSF
bull At present NO nucleoprotein sequences unique to pathogenic FCoV (ie not also present in nonpathogenic FCoV) have been identified
FCoV FECV FCoV where are they
Small intestinal enterocytes
Colon -rectum
Healthy shedders
Asymptomatic or mild diarrhea
After clearance from sm intestine FCoVs spread to infect colon and intermittently shedded off
If kittens infected before immune system fully mature levels of FECV replication will be very high
Reinfection may be from FCoV same strains or different strains
Pyogranulomatous inflammation
FIPV infected monocytes perivascular macrophages overproduce neutrophil survival factors Tumor necrosis factor- alpha (TNF ndashalpha) bull Matrix metalloproyeinase-9 bull GM-CSF bull G-CSF Neutrophil survival Development of granuloma lesions
Interpretation of FCoV antibody test
Viral shedding ~ 2 days (FCoV in epithelial cells)
Signs of FIP
bull As early as 2 wk old to 18 months
bull From pyogranulomatous inflammation to clinical signs may be months
From NC Pederson et al (2008) Feline enteric coronavirus infection
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To rule out FIP in sick cats bull effusive FIP
bull non- effusive FIP ( esp cats with GI signs)
bull To screen the FCoV excretors bull Cats in contact with known FCoV shedder
bull Cats in the household
bull New kitten or new cat bringing into the multi-cat household
bull Before receiving immunosuppressive treatment or stressful procedures
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To screen a breeding queen
bull To monitor FIP treatment q 8-12 wks
bull To screen blood donor cat
bull To screen prior to FeLV vaccination
Blood fluid Interpretation of FCoV antibody test
I false negative in sick FIP cat
II High titer (gt 11600) in normal cat (esp cat from multi-household) is not indicated FIP
III High titer in fluid high PPV
IV Generally not recommended in sick cat
FCoV antibody in CSF
bull Use of anti-coronavirus antibody testing of cerebrospinal fluid for diagnosis of feline infectious peritonitis involving the central nervous system in cats
bull J Am Vet Med Assoc January 2007230(2)199-205
bull Irene C Boettcher1 Tanja Steinberg Kaspar Matiasek Craig E Greene Katrin Hartmann Andrea Fischer
CSF IgG was detected only in strongly seropositive cats suggested that CSF anti-coronavirus IgG was derived from blood Measurement of
anti-coronavirus IgG in CSF was of equivocal clinical use
Test test test
FCoV RT-PCR test ( bloodeffusion fluidfeces)
Blood FCoV RT-PCR FECV Monocyte-associated viremia Not differentiate FIPV from pathotype
FCoV
Fecal FCoV RT-PC Recommend for house-cat management BUT single positive or negative tests are
meaningless as cats may shed intermittently or may be recently infected
Effusion fluid FCoV RT-PCR bull Generally recommended for fluid bull Positive result high PPV bull But 30 of effusions from cats
with FIP may be negative by RT-PCR
Why false negative 1 FIPV is cell-associated and likely confined to cells of perivascular granuloma (leaking out of pure plasma) 2 Inhibition of RT-PCR by interfering substances in fluid Therefore negative result doesnrsquot exclude FIP
Is FIP a contagious disease (cat-to-cat transmission)
Is FIP a contagious disease (cat-to-cat transmission)
Cats with FIP do not excrete pathogenic FIPV
FECV in enterocytes
Is FIP contagious
Cats with FIP do not appear to be very contagious to cats coming in contact with
Every FIPV isolated from a group outbreak of FIP does NOT genetically identical in its 3c gene mutation
However FIPV is found in the feces of most cats with FIP
Mutation when FECV turns into FIPV
Internal mutation theory bull Genetic changes from FECV
to FIPV
bull Various types of mutation within OPFs 3 and 7
bull 20 of kittens infected with FECV will produce an FIP mutant
Horizontal (cat-to cat) bull Transmission of FIPV
mutants
bull cats with FIP are shedding the same FIPV in their feces
J Gen Virol 2010 Feb91(Pt 2)415-20 doi 101099vir0016485-0 Epub 2009 Nov 4
Feline infectious peritonitis insights into feline coronavirus
pathobiogenesis and epidemiology based on genetic analysis of the viral
3c gene Chang HW1 de Groot RJ Egberink HF Rottier PJ
helliphellipMost cats with FIP had no detectable intestinal feline coronaviruses (FCoVs) and
had seemingly cleared the primary FECV infection In those with detectable intestinal
FCoV the virus always had an intact 3c and seemed to have been acquired by FECV
superinfection Apparently 3c-inactivated viruses replicate not at all--or only poorly--in the
gut explaining the rare incidence of FIP outbreaks
FIP transmission
FIP transmission
bull Vet Res 2013 Jul 174457 doi 1011861297-9716-44-57
bull An outbreak of feline infectious peritonitis in a Taiwanese shelter epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus
bull Wang YT1 Su BL Hsieh LE Chueh LL
bull Abstract
bull helliphellipSequence analysis revealed that the type II FIPV detected from fecal samples body
effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death Taken together our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment
FCoV field strain in FIP cat
Genomic RNA sequence of feline coronavirus strain FCoV C1Je Charlotte Dye BVMampS PhD CertSAM MRCVS
Stuart G Siddell BSc(Hons) PhD
bull This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV) Viral RNAs isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP) derived 100 nucleotide identity
Feline Coronavirus serotypes I and II were reported in natural infection
bull Feline coronavirus serotypes 1 and 2 seroprevalence and association with disease in Switzerland
bull Clin Diagn Lab Immunol October 200512(10)1209-15 bull Maya Kummrow1 Marina L Meli Michael Haessig Enikoe Goenczi Amy Poland Niels C
Pedersen Regina Hofmann-Lehmann Hans Lutz
bull Comparison of serologic techniques for the detection of antibodies against feline coronaviruses
bull J Vet Diagn Invest January 200820(1)45-50 bull Annamaria Pratelli1
bull Prevalence of Korean cats with natural feline coronavirus infections bull Virol J January 20118(0)455 bull Dong-Jun An1 Hye-Young Jeoung Wooseog Jeong Jee Yong Park Myoung-Heon Lee Bong
Kyun Park bull 1National Veterinary Research and Quarantine Service Anyang Kyunggi-do430-824 Korea
bull Moreshellip
Take home message Knowing ME knowing YOU
My team my world
Thank you
Prevalence of Feline Coronaviruses (FCoV)
Housed cats
bull 25-40 of cats infected with FCoV
Multi cat household colonies
bull 80-100 of cats infected with FCoV
In high prevalent area occurrence of FIP ~ 10
How FECV turn into FIPV
bull Two theories
ndash Internal mutation
ndash Circulating virulent avirulent viruses
bull FIPV and FECV strains can be serotpye I or II
Mutation when FECV turns into FIPV
Internal mutation theory
bull Genetic changes from FECV to FIPV in individual infected cat
bull Various types of mutation within 3c gene
bull 20 of kittens infected with FECV will produce an FIP mutant
Molecular Studies for diagnosis of FIP
bull Conflicting results
bull FCoV 1 (FIPV I) hellipvirulent bull FCoV II (FIPV II)hellipnon-virulent
Pathogenesis of FIP controversial
bull Immune-mediated vasculitis
bull Immune complex Type 3 hypersensitivity disease
Ag + Ab +compliments +C3
bull Pathological morphology
ndash Activation of monocytes
macrophages
ndash Monocyte-mediated viremia
ndash Granulomatous phleblitis periphlebitis
ndash VEGF ndash mediators increase vascular permeability
Endothelial cells show strongly MHCII antigen positive
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Activated macrophages
Morphologic Features and Development of Granulomatous vasculitis in FIP Kipar et al(2005)
Emigration of FCoV ndashinfected monocytes to vascular perivascular granulomatous infiltrates
with destruction of vascular basal laminar
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Leptomeningeal veins Agglomerate of TNF-α-positive monocytes attached to
venous endothelium Avidin-biotin-peroxidase complex method Papanicolaous hematoxylin counterstain Bar = 10 μm
Objective bullKnowing FCoVs
bullFCoVs in clinical diagnosis
Serology and Molecular diagnosis
Indirect FCoV antibody test Direct (viral load) FCoV RT-PCR
bull Blood
bull Feces
bull Effusion fluid
bull CSF
bull At present NO nucleoprotein sequences unique to pathogenic FCoV (ie not also present in nonpathogenic FCoV) have been identified
FCoV FECV FCoV where are they
Small intestinal enterocytes
Colon -rectum
Healthy shedders
Asymptomatic or mild diarrhea
After clearance from sm intestine FCoVs spread to infect colon and intermittently shedded off
If kittens infected before immune system fully mature levels of FECV replication will be very high
Reinfection may be from FCoV same strains or different strains
Pyogranulomatous inflammation
FIPV infected monocytes perivascular macrophages overproduce neutrophil survival factors Tumor necrosis factor- alpha (TNF ndashalpha) bull Matrix metalloproyeinase-9 bull GM-CSF bull G-CSF Neutrophil survival Development of granuloma lesions
Interpretation of FCoV antibody test
Viral shedding ~ 2 days (FCoV in epithelial cells)
Signs of FIP
bull As early as 2 wk old to 18 months
bull From pyogranulomatous inflammation to clinical signs may be months
From NC Pederson et al (2008) Feline enteric coronavirus infection
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To rule out FIP in sick cats bull effusive FIP
bull non- effusive FIP ( esp cats with GI signs)
bull To screen the FCoV excretors bull Cats in contact with known FCoV shedder
bull Cats in the household
bull New kitten or new cat bringing into the multi-cat household
bull Before receiving immunosuppressive treatment or stressful procedures
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To screen a breeding queen
bull To monitor FIP treatment q 8-12 wks
bull To screen blood donor cat
bull To screen prior to FeLV vaccination
Blood fluid Interpretation of FCoV antibody test
I false negative in sick FIP cat
II High titer (gt 11600) in normal cat (esp cat from multi-household) is not indicated FIP
III High titer in fluid high PPV
IV Generally not recommended in sick cat
FCoV antibody in CSF
bull Use of anti-coronavirus antibody testing of cerebrospinal fluid for diagnosis of feline infectious peritonitis involving the central nervous system in cats
bull J Am Vet Med Assoc January 2007230(2)199-205
bull Irene C Boettcher1 Tanja Steinberg Kaspar Matiasek Craig E Greene Katrin Hartmann Andrea Fischer
CSF IgG was detected only in strongly seropositive cats suggested that CSF anti-coronavirus IgG was derived from blood Measurement of
anti-coronavirus IgG in CSF was of equivocal clinical use
Test test test
FCoV RT-PCR test ( bloodeffusion fluidfeces)
Blood FCoV RT-PCR FECV Monocyte-associated viremia Not differentiate FIPV from pathotype
FCoV
Fecal FCoV RT-PC Recommend for house-cat management BUT single positive or negative tests are
meaningless as cats may shed intermittently or may be recently infected
Effusion fluid FCoV RT-PCR bull Generally recommended for fluid bull Positive result high PPV bull But 30 of effusions from cats
with FIP may be negative by RT-PCR
Why false negative 1 FIPV is cell-associated and likely confined to cells of perivascular granuloma (leaking out of pure plasma) 2 Inhibition of RT-PCR by interfering substances in fluid Therefore negative result doesnrsquot exclude FIP
Is FIP a contagious disease (cat-to-cat transmission)
Is FIP a contagious disease (cat-to-cat transmission)
Cats with FIP do not excrete pathogenic FIPV
FECV in enterocytes
Is FIP contagious
Cats with FIP do not appear to be very contagious to cats coming in contact with
Every FIPV isolated from a group outbreak of FIP does NOT genetically identical in its 3c gene mutation
However FIPV is found in the feces of most cats with FIP
Mutation when FECV turns into FIPV
Internal mutation theory bull Genetic changes from FECV
to FIPV
bull Various types of mutation within OPFs 3 and 7
bull 20 of kittens infected with FECV will produce an FIP mutant
Horizontal (cat-to cat) bull Transmission of FIPV
mutants
bull cats with FIP are shedding the same FIPV in their feces
J Gen Virol 2010 Feb91(Pt 2)415-20 doi 101099vir0016485-0 Epub 2009 Nov 4
Feline infectious peritonitis insights into feline coronavirus
pathobiogenesis and epidemiology based on genetic analysis of the viral
3c gene Chang HW1 de Groot RJ Egberink HF Rottier PJ
helliphellipMost cats with FIP had no detectable intestinal feline coronaviruses (FCoVs) and
had seemingly cleared the primary FECV infection In those with detectable intestinal
FCoV the virus always had an intact 3c and seemed to have been acquired by FECV
superinfection Apparently 3c-inactivated viruses replicate not at all--or only poorly--in the
gut explaining the rare incidence of FIP outbreaks
FIP transmission
FIP transmission
bull Vet Res 2013 Jul 174457 doi 1011861297-9716-44-57
bull An outbreak of feline infectious peritonitis in a Taiwanese shelter epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus
bull Wang YT1 Su BL Hsieh LE Chueh LL
bull Abstract
bull helliphellipSequence analysis revealed that the type II FIPV detected from fecal samples body
effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death Taken together our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment
FCoV field strain in FIP cat
Genomic RNA sequence of feline coronavirus strain FCoV C1Je Charlotte Dye BVMampS PhD CertSAM MRCVS
Stuart G Siddell BSc(Hons) PhD
bull This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV) Viral RNAs isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP) derived 100 nucleotide identity
Feline Coronavirus serotypes I and II were reported in natural infection
bull Feline coronavirus serotypes 1 and 2 seroprevalence and association with disease in Switzerland
bull Clin Diagn Lab Immunol October 200512(10)1209-15 bull Maya Kummrow1 Marina L Meli Michael Haessig Enikoe Goenczi Amy Poland Niels C
Pedersen Regina Hofmann-Lehmann Hans Lutz
bull Comparison of serologic techniques for the detection of antibodies against feline coronaviruses
bull J Vet Diagn Invest January 200820(1)45-50 bull Annamaria Pratelli1
bull Prevalence of Korean cats with natural feline coronavirus infections bull Virol J January 20118(0)455 bull Dong-Jun An1 Hye-Young Jeoung Wooseog Jeong Jee Yong Park Myoung-Heon Lee Bong
Kyun Park bull 1National Veterinary Research and Quarantine Service Anyang Kyunggi-do430-824 Korea
bull Moreshellip
Take home message Knowing ME knowing YOU
My team my world
Thank you
How FECV turn into FIPV
bull Two theories
ndash Internal mutation
ndash Circulating virulent avirulent viruses
bull FIPV and FECV strains can be serotpye I or II
Mutation when FECV turns into FIPV
Internal mutation theory
bull Genetic changes from FECV to FIPV in individual infected cat
bull Various types of mutation within 3c gene
bull 20 of kittens infected with FECV will produce an FIP mutant
Molecular Studies for diagnosis of FIP
bull Conflicting results
bull FCoV 1 (FIPV I) hellipvirulent bull FCoV II (FIPV II)hellipnon-virulent
Pathogenesis of FIP controversial
bull Immune-mediated vasculitis
bull Immune complex Type 3 hypersensitivity disease
Ag + Ab +compliments +C3
bull Pathological morphology
ndash Activation of monocytes
macrophages
ndash Monocyte-mediated viremia
ndash Granulomatous phleblitis periphlebitis
ndash VEGF ndash mediators increase vascular permeability
Endothelial cells show strongly MHCII antigen positive
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Activated macrophages
Morphologic Features and Development of Granulomatous vasculitis in FIP Kipar et al(2005)
Emigration of FCoV ndashinfected monocytes to vascular perivascular granulomatous infiltrates
with destruction of vascular basal laminar
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Leptomeningeal veins Agglomerate of TNF-α-positive monocytes attached to
venous endothelium Avidin-biotin-peroxidase complex method Papanicolaous hematoxylin counterstain Bar = 10 μm
Objective bullKnowing FCoVs
bullFCoVs in clinical diagnosis
Serology and Molecular diagnosis
Indirect FCoV antibody test Direct (viral load) FCoV RT-PCR
bull Blood
bull Feces
bull Effusion fluid
bull CSF
bull At present NO nucleoprotein sequences unique to pathogenic FCoV (ie not also present in nonpathogenic FCoV) have been identified
FCoV FECV FCoV where are they
Small intestinal enterocytes
Colon -rectum
Healthy shedders
Asymptomatic or mild diarrhea
After clearance from sm intestine FCoVs spread to infect colon and intermittently shedded off
If kittens infected before immune system fully mature levels of FECV replication will be very high
Reinfection may be from FCoV same strains or different strains
Pyogranulomatous inflammation
FIPV infected monocytes perivascular macrophages overproduce neutrophil survival factors Tumor necrosis factor- alpha (TNF ndashalpha) bull Matrix metalloproyeinase-9 bull GM-CSF bull G-CSF Neutrophil survival Development of granuloma lesions
Interpretation of FCoV antibody test
Viral shedding ~ 2 days (FCoV in epithelial cells)
Signs of FIP
bull As early as 2 wk old to 18 months
bull From pyogranulomatous inflammation to clinical signs may be months
From NC Pederson et al (2008) Feline enteric coronavirus infection
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To rule out FIP in sick cats bull effusive FIP
bull non- effusive FIP ( esp cats with GI signs)
bull To screen the FCoV excretors bull Cats in contact with known FCoV shedder
bull Cats in the household
bull New kitten or new cat bringing into the multi-cat household
bull Before receiving immunosuppressive treatment or stressful procedures
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To screen a breeding queen
bull To monitor FIP treatment q 8-12 wks
bull To screen blood donor cat
bull To screen prior to FeLV vaccination
Blood fluid Interpretation of FCoV antibody test
I false negative in sick FIP cat
II High titer (gt 11600) in normal cat (esp cat from multi-household) is not indicated FIP
III High titer in fluid high PPV
IV Generally not recommended in sick cat
FCoV antibody in CSF
bull Use of anti-coronavirus antibody testing of cerebrospinal fluid for diagnosis of feline infectious peritonitis involving the central nervous system in cats
bull J Am Vet Med Assoc January 2007230(2)199-205
bull Irene C Boettcher1 Tanja Steinberg Kaspar Matiasek Craig E Greene Katrin Hartmann Andrea Fischer
CSF IgG was detected only in strongly seropositive cats suggested that CSF anti-coronavirus IgG was derived from blood Measurement of
anti-coronavirus IgG in CSF was of equivocal clinical use
Test test test
FCoV RT-PCR test ( bloodeffusion fluidfeces)
Blood FCoV RT-PCR FECV Monocyte-associated viremia Not differentiate FIPV from pathotype
FCoV
Fecal FCoV RT-PC Recommend for house-cat management BUT single positive or negative tests are
meaningless as cats may shed intermittently or may be recently infected
Effusion fluid FCoV RT-PCR bull Generally recommended for fluid bull Positive result high PPV bull But 30 of effusions from cats
with FIP may be negative by RT-PCR
Why false negative 1 FIPV is cell-associated and likely confined to cells of perivascular granuloma (leaking out of pure plasma) 2 Inhibition of RT-PCR by interfering substances in fluid Therefore negative result doesnrsquot exclude FIP
Is FIP a contagious disease (cat-to-cat transmission)
Is FIP a contagious disease (cat-to-cat transmission)
Cats with FIP do not excrete pathogenic FIPV
FECV in enterocytes
Is FIP contagious
Cats with FIP do not appear to be very contagious to cats coming in contact with
Every FIPV isolated from a group outbreak of FIP does NOT genetically identical in its 3c gene mutation
However FIPV is found in the feces of most cats with FIP
Mutation when FECV turns into FIPV
Internal mutation theory bull Genetic changes from FECV
to FIPV
bull Various types of mutation within OPFs 3 and 7
bull 20 of kittens infected with FECV will produce an FIP mutant
Horizontal (cat-to cat) bull Transmission of FIPV
mutants
bull cats with FIP are shedding the same FIPV in their feces
J Gen Virol 2010 Feb91(Pt 2)415-20 doi 101099vir0016485-0 Epub 2009 Nov 4
Feline infectious peritonitis insights into feline coronavirus
pathobiogenesis and epidemiology based on genetic analysis of the viral
3c gene Chang HW1 de Groot RJ Egberink HF Rottier PJ
helliphellipMost cats with FIP had no detectable intestinal feline coronaviruses (FCoVs) and
had seemingly cleared the primary FECV infection In those with detectable intestinal
FCoV the virus always had an intact 3c and seemed to have been acquired by FECV
superinfection Apparently 3c-inactivated viruses replicate not at all--or only poorly--in the
gut explaining the rare incidence of FIP outbreaks
FIP transmission
FIP transmission
bull Vet Res 2013 Jul 174457 doi 1011861297-9716-44-57
bull An outbreak of feline infectious peritonitis in a Taiwanese shelter epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus
bull Wang YT1 Su BL Hsieh LE Chueh LL
bull Abstract
bull helliphellipSequence analysis revealed that the type II FIPV detected from fecal samples body
effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death Taken together our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment
FCoV field strain in FIP cat
Genomic RNA sequence of feline coronavirus strain FCoV C1Je Charlotte Dye BVMampS PhD CertSAM MRCVS
Stuart G Siddell BSc(Hons) PhD
bull This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV) Viral RNAs isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP) derived 100 nucleotide identity
Feline Coronavirus serotypes I and II were reported in natural infection
bull Feline coronavirus serotypes 1 and 2 seroprevalence and association with disease in Switzerland
bull Clin Diagn Lab Immunol October 200512(10)1209-15 bull Maya Kummrow1 Marina L Meli Michael Haessig Enikoe Goenczi Amy Poland Niels C
Pedersen Regina Hofmann-Lehmann Hans Lutz
bull Comparison of serologic techniques for the detection of antibodies against feline coronaviruses
bull J Vet Diagn Invest January 200820(1)45-50 bull Annamaria Pratelli1
bull Prevalence of Korean cats with natural feline coronavirus infections bull Virol J January 20118(0)455 bull Dong-Jun An1 Hye-Young Jeoung Wooseog Jeong Jee Yong Park Myoung-Heon Lee Bong
Kyun Park bull 1National Veterinary Research and Quarantine Service Anyang Kyunggi-do430-824 Korea
bull Moreshellip
Take home message Knowing ME knowing YOU
My team my world
Thank you
Mutation when FECV turns into FIPV
Internal mutation theory
bull Genetic changes from FECV to FIPV in individual infected cat
bull Various types of mutation within 3c gene
bull 20 of kittens infected with FECV will produce an FIP mutant
Molecular Studies for diagnosis of FIP
bull Conflicting results
bull FCoV 1 (FIPV I) hellipvirulent bull FCoV II (FIPV II)hellipnon-virulent
Pathogenesis of FIP controversial
bull Immune-mediated vasculitis
bull Immune complex Type 3 hypersensitivity disease
Ag + Ab +compliments +C3
bull Pathological morphology
ndash Activation of monocytes
macrophages
ndash Monocyte-mediated viremia
ndash Granulomatous phleblitis periphlebitis
ndash VEGF ndash mediators increase vascular permeability
Endothelial cells show strongly MHCII antigen positive
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Activated macrophages
Morphologic Features and Development of Granulomatous vasculitis in FIP Kipar et al(2005)
Emigration of FCoV ndashinfected monocytes to vascular perivascular granulomatous infiltrates
with destruction of vascular basal laminar
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Leptomeningeal veins Agglomerate of TNF-α-positive monocytes attached to
venous endothelium Avidin-biotin-peroxidase complex method Papanicolaous hematoxylin counterstain Bar = 10 μm
Objective bullKnowing FCoVs
bullFCoVs in clinical diagnosis
Serology and Molecular diagnosis
Indirect FCoV antibody test Direct (viral load) FCoV RT-PCR
bull Blood
bull Feces
bull Effusion fluid
bull CSF
bull At present NO nucleoprotein sequences unique to pathogenic FCoV (ie not also present in nonpathogenic FCoV) have been identified
FCoV FECV FCoV where are they
Small intestinal enterocytes
Colon -rectum
Healthy shedders
Asymptomatic or mild diarrhea
After clearance from sm intestine FCoVs spread to infect colon and intermittently shedded off
If kittens infected before immune system fully mature levels of FECV replication will be very high
Reinfection may be from FCoV same strains or different strains
Pyogranulomatous inflammation
FIPV infected monocytes perivascular macrophages overproduce neutrophil survival factors Tumor necrosis factor- alpha (TNF ndashalpha) bull Matrix metalloproyeinase-9 bull GM-CSF bull G-CSF Neutrophil survival Development of granuloma lesions
Interpretation of FCoV antibody test
Viral shedding ~ 2 days (FCoV in epithelial cells)
Signs of FIP
bull As early as 2 wk old to 18 months
bull From pyogranulomatous inflammation to clinical signs may be months
From NC Pederson et al (2008) Feline enteric coronavirus infection
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To rule out FIP in sick cats bull effusive FIP
bull non- effusive FIP ( esp cats with GI signs)
bull To screen the FCoV excretors bull Cats in contact with known FCoV shedder
bull Cats in the household
bull New kitten or new cat bringing into the multi-cat household
bull Before receiving immunosuppressive treatment or stressful procedures
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To screen a breeding queen
bull To monitor FIP treatment q 8-12 wks
bull To screen blood donor cat
bull To screen prior to FeLV vaccination
Blood fluid Interpretation of FCoV antibody test
I false negative in sick FIP cat
II High titer (gt 11600) in normal cat (esp cat from multi-household) is not indicated FIP
III High titer in fluid high PPV
IV Generally not recommended in sick cat
FCoV antibody in CSF
bull Use of anti-coronavirus antibody testing of cerebrospinal fluid for diagnosis of feline infectious peritonitis involving the central nervous system in cats
bull J Am Vet Med Assoc January 2007230(2)199-205
bull Irene C Boettcher1 Tanja Steinberg Kaspar Matiasek Craig E Greene Katrin Hartmann Andrea Fischer
CSF IgG was detected only in strongly seropositive cats suggested that CSF anti-coronavirus IgG was derived from blood Measurement of
anti-coronavirus IgG in CSF was of equivocal clinical use
Test test test
FCoV RT-PCR test ( bloodeffusion fluidfeces)
Blood FCoV RT-PCR FECV Monocyte-associated viremia Not differentiate FIPV from pathotype
FCoV
Fecal FCoV RT-PC Recommend for house-cat management BUT single positive or negative tests are
meaningless as cats may shed intermittently or may be recently infected
Effusion fluid FCoV RT-PCR bull Generally recommended for fluid bull Positive result high PPV bull But 30 of effusions from cats
with FIP may be negative by RT-PCR
Why false negative 1 FIPV is cell-associated and likely confined to cells of perivascular granuloma (leaking out of pure plasma) 2 Inhibition of RT-PCR by interfering substances in fluid Therefore negative result doesnrsquot exclude FIP
Is FIP a contagious disease (cat-to-cat transmission)
Is FIP a contagious disease (cat-to-cat transmission)
Cats with FIP do not excrete pathogenic FIPV
FECV in enterocytes
Is FIP contagious
Cats with FIP do not appear to be very contagious to cats coming in contact with
Every FIPV isolated from a group outbreak of FIP does NOT genetically identical in its 3c gene mutation
However FIPV is found in the feces of most cats with FIP
Mutation when FECV turns into FIPV
Internal mutation theory bull Genetic changes from FECV
to FIPV
bull Various types of mutation within OPFs 3 and 7
bull 20 of kittens infected with FECV will produce an FIP mutant
Horizontal (cat-to cat) bull Transmission of FIPV
mutants
bull cats with FIP are shedding the same FIPV in their feces
J Gen Virol 2010 Feb91(Pt 2)415-20 doi 101099vir0016485-0 Epub 2009 Nov 4
Feline infectious peritonitis insights into feline coronavirus
pathobiogenesis and epidemiology based on genetic analysis of the viral
3c gene Chang HW1 de Groot RJ Egberink HF Rottier PJ
helliphellipMost cats with FIP had no detectable intestinal feline coronaviruses (FCoVs) and
had seemingly cleared the primary FECV infection In those with detectable intestinal
FCoV the virus always had an intact 3c and seemed to have been acquired by FECV
superinfection Apparently 3c-inactivated viruses replicate not at all--or only poorly--in the
gut explaining the rare incidence of FIP outbreaks
FIP transmission
FIP transmission
bull Vet Res 2013 Jul 174457 doi 1011861297-9716-44-57
bull An outbreak of feline infectious peritonitis in a Taiwanese shelter epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus
bull Wang YT1 Su BL Hsieh LE Chueh LL
bull Abstract
bull helliphellipSequence analysis revealed that the type II FIPV detected from fecal samples body
effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death Taken together our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment
FCoV field strain in FIP cat
Genomic RNA sequence of feline coronavirus strain FCoV C1Je Charlotte Dye BVMampS PhD CertSAM MRCVS
Stuart G Siddell BSc(Hons) PhD
bull This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV) Viral RNAs isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP) derived 100 nucleotide identity
Feline Coronavirus serotypes I and II were reported in natural infection
bull Feline coronavirus serotypes 1 and 2 seroprevalence and association with disease in Switzerland
bull Clin Diagn Lab Immunol October 200512(10)1209-15 bull Maya Kummrow1 Marina L Meli Michael Haessig Enikoe Goenczi Amy Poland Niels C
Pedersen Regina Hofmann-Lehmann Hans Lutz
bull Comparison of serologic techniques for the detection of antibodies against feline coronaviruses
bull J Vet Diagn Invest January 200820(1)45-50 bull Annamaria Pratelli1
bull Prevalence of Korean cats with natural feline coronavirus infections bull Virol J January 20118(0)455 bull Dong-Jun An1 Hye-Young Jeoung Wooseog Jeong Jee Yong Park Myoung-Heon Lee Bong
Kyun Park bull 1National Veterinary Research and Quarantine Service Anyang Kyunggi-do430-824 Korea
bull Moreshellip
Take home message Knowing ME knowing YOU
My team my world
Thank you
Molecular Studies for diagnosis of FIP
bull Conflicting results
bull FCoV 1 (FIPV I) hellipvirulent bull FCoV II (FIPV II)hellipnon-virulent
Pathogenesis of FIP controversial
bull Immune-mediated vasculitis
bull Immune complex Type 3 hypersensitivity disease
Ag + Ab +compliments +C3
bull Pathological morphology
ndash Activation of monocytes
macrophages
ndash Monocyte-mediated viremia
ndash Granulomatous phleblitis periphlebitis
ndash VEGF ndash mediators increase vascular permeability
Endothelial cells show strongly MHCII antigen positive
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Activated macrophages
Morphologic Features and Development of Granulomatous vasculitis in FIP Kipar et al(2005)
Emigration of FCoV ndashinfected monocytes to vascular perivascular granulomatous infiltrates
with destruction of vascular basal laminar
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Leptomeningeal veins Agglomerate of TNF-α-positive monocytes attached to
venous endothelium Avidin-biotin-peroxidase complex method Papanicolaous hematoxylin counterstain Bar = 10 μm
Objective bullKnowing FCoVs
bullFCoVs in clinical diagnosis
Serology and Molecular diagnosis
Indirect FCoV antibody test Direct (viral load) FCoV RT-PCR
bull Blood
bull Feces
bull Effusion fluid
bull CSF
bull At present NO nucleoprotein sequences unique to pathogenic FCoV (ie not also present in nonpathogenic FCoV) have been identified
FCoV FECV FCoV where are they
Small intestinal enterocytes
Colon -rectum
Healthy shedders
Asymptomatic or mild diarrhea
After clearance from sm intestine FCoVs spread to infect colon and intermittently shedded off
If kittens infected before immune system fully mature levels of FECV replication will be very high
Reinfection may be from FCoV same strains or different strains
Pyogranulomatous inflammation
FIPV infected monocytes perivascular macrophages overproduce neutrophil survival factors Tumor necrosis factor- alpha (TNF ndashalpha) bull Matrix metalloproyeinase-9 bull GM-CSF bull G-CSF Neutrophil survival Development of granuloma lesions
Interpretation of FCoV antibody test
Viral shedding ~ 2 days (FCoV in epithelial cells)
Signs of FIP
bull As early as 2 wk old to 18 months
bull From pyogranulomatous inflammation to clinical signs may be months
From NC Pederson et al (2008) Feline enteric coronavirus infection
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To rule out FIP in sick cats bull effusive FIP
bull non- effusive FIP ( esp cats with GI signs)
bull To screen the FCoV excretors bull Cats in contact with known FCoV shedder
bull Cats in the household
bull New kitten or new cat bringing into the multi-cat household
bull Before receiving immunosuppressive treatment or stressful procedures
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To screen a breeding queen
bull To monitor FIP treatment q 8-12 wks
bull To screen blood donor cat
bull To screen prior to FeLV vaccination
Blood fluid Interpretation of FCoV antibody test
I false negative in sick FIP cat
II High titer (gt 11600) in normal cat (esp cat from multi-household) is not indicated FIP
III High titer in fluid high PPV
IV Generally not recommended in sick cat
FCoV antibody in CSF
bull Use of anti-coronavirus antibody testing of cerebrospinal fluid for diagnosis of feline infectious peritonitis involving the central nervous system in cats
bull J Am Vet Med Assoc January 2007230(2)199-205
bull Irene C Boettcher1 Tanja Steinberg Kaspar Matiasek Craig E Greene Katrin Hartmann Andrea Fischer
CSF IgG was detected only in strongly seropositive cats suggested that CSF anti-coronavirus IgG was derived from blood Measurement of
anti-coronavirus IgG in CSF was of equivocal clinical use
Test test test
FCoV RT-PCR test ( bloodeffusion fluidfeces)
Blood FCoV RT-PCR FECV Monocyte-associated viremia Not differentiate FIPV from pathotype
FCoV
Fecal FCoV RT-PC Recommend for house-cat management BUT single positive or negative tests are
meaningless as cats may shed intermittently or may be recently infected
Effusion fluid FCoV RT-PCR bull Generally recommended for fluid bull Positive result high PPV bull But 30 of effusions from cats
with FIP may be negative by RT-PCR
Why false negative 1 FIPV is cell-associated and likely confined to cells of perivascular granuloma (leaking out of pure plasma) 2 Inhibition of RT-PCR by interfering substances in fluid Therefore negative result doesnrsquot exclude FIP
Is FIP a contagious disease (cat-to-cat transmission)
Is FIP a contagious disease (cat-to-cat transmission)
Cats with FIP do not excrete pathogenic FIPV
FECV in enterocytes
Is FIP contagious
Cats with FIP do not appear to be very contagious to cats coming in contact with
Every FIPV isolated from a group outbreak of FIP does NOT genetically identical in its 3c gene mutation
However FIPV is found in the feces of most cats with FIP
Mutation when FECV turns into FIPV
Internal mutation theory bull Genetic changes from FECV
to FIPV
bull Various types of mutation within OPFs 3 and 7
bull 20 of kittens infected with FECV will produce an FIP mutant
Horizontal (cat-to cat) bull Transmission of FIPV
mutants
bull cats with FIP are shedding the same FIPV in their feces
J Gen Virol 2010 Feb91(Pt 2)415-20 doi 101099vir0016485-0 Epub 2009 Nov 4
Feline infectious peritonitis insights into feline coronavirus
pathobiogenesis and epidemiology based on genetic analysis of the viral
3c gene Chang HW1 de Groot RJ Egberink HF Rottier PJ
helliphellipMost cats with FIP had no detectable intestinal feline coronaviruses (FCoVs) and
had seemingly cleared the primary FECV infection In those with detectable intestinal
FCoV the virus always had an intact 3c and seemed to have been acquired by FECV
superinfection Apparently 3c-inactivated viruses replicate not at all--or only poorly--in the
gut explaining the rare incidence of FIP outbreaks
FIP transmission
FIP transmission
bull Vet Res 2013 Jul 174457 doi 1011861297-9716-44-57
bull An outbreak of feline infectious peritonitis in a Taiwanese shelter epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus
bull Wang YT1 Su BL Hsieh LE Chueh LL
bull Abstract
bull helliphellipSequence analysis revealed that the type II FIPV detected from fecal samples body
effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death Taken together our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment
FCoV field strain in FIP cat
Genomic RNA sequence of feline coronavirus strain FCoV C1Je Charlotte Dye BVMampS PhD CertSAM MRCVS
Stuart G Siddell BSc(Hons) PhD
bull This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV) Viral RNAs isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP) derived 100 nucleotide identity
Feline Coronavirus serotypes I and II were reported in natural infection
bull Feline coronavirus serotypes 1 and 2 seroprevalence and association with disease in Switzerland
bull Clin Diagn Lab Immunol October 200512(10)1209-15 bull Maya Kummrow1 Marina L Meli Michael Haessig Enikoe Goenczi Amy Poland Niels C
Pedersen Regina Hofmann-Lehmann Hans Lutz
bull Comparison of serologic techniques for the detection of antibodies against feline coronaviruses
bull J Vet Diagn Invest January 200820(1)45-50 bull Annamaria Pratelli1
bull Prevalence of Korean cats with natural feline coronavirus infections bull Virol J January 20118(0)455 bull Dong-Jun An1 Hye-Young Jeoung Wooseog Jeong Jee Yong Park Myoung-Heon Lee Bong
Kyun Park bull 1National Veterinary Research and Quarantine Service Anyang Kyunggi-do430-824 Korea
bull Moreshellip
Take home message Knowing ME knowing YOU
My team my world
Thank you
Pathogenesis of FIP controversial
bull Immune-mediated vasculitis
bull Immune complex Type 3 hypersensitivity disease
Ag + Ab +compliments +C3
bull Pathological morphology
ndash Activation of monocytes
macrophages
ndash Monocyte-mediated viremia
ndash Granulomatous phleblitis periphlebitis
ndash VEGF ndash mediators increase vascular permeability
Endothelial cells show strongly MHCII antigen positive
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Activated macrophages
Morphologic Features and Development of Granulomatous vasculitis in FIP Kipar et al(2005)
Emigration of FCoV ndashinfected monocytes to vascular perivascular granulomatous infiltrates
with destruction of vascular basal laminar
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Leptomeningeal veins Agglomerate of TNF-α-positive monocytes attached to
venous endothelium Avidin-biotin-peroxidase complex method Papanicolaous hematoxylin counterstain Bar = 10 μm
Objective bullKnowing FCoVs
bullFCoVs in clinical diagnosis
Serology and Molecular diagnosis
Indirect FCoV antibody test Direct (viral load) FCoV RT-PCR
bull Blood
bull Feces
bull Effusion fluid
bull CSF
bull At present NO nucleoprotein sequences unique to pathogenic FCoV (ie not also present in nonpathogenic FCoV) have been identified
FCoV FECV FCoV where are they
Small intestinal enterocytes
Colon -rectum
Healthy shedders
Asymptomatic or mild diarrhea
After clearance from sm intestine FCoVs spread to infect colon and intermittently shedded off
If kittens infected before immune system fully mature levels of FECV replication will be very high
Reinfection may be from FCoV same strains or different strains
Pyogranulomatous inflammation
FIPV infected monocytes perivascular macrophages overproduce neutrophil survival factors Tumor necrosis factor- alpha (TNF ndashalpha) bull Matrix metalloproyeinase-9 bull GM-CSF bull G-CSF Neutrophil survival Development of granuloma lesions
Interpretation of FCoV antibody test
Viral shedding ~ 2 days (FCoV in epithelial cells)
Signs of FIP
bull As early as 2 wk old to 18 months
bull From pyogranulomatous inflammation to clinical signs may be months
From NC Pederson et al (2008) Feline enteric coronavirus infection
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To rule out FIP in sick cats bull effusive FIP
bull non- effusive FIP ( esp cats with GI signs)
bull To screen the FCoV excretors bull Cats in contact with known FCoV shedder
bull Cats in the household
bull New kitten or new cat bringing into the multi-cat household
bull Before receiving immunosuppressive treatment or stressful procedures
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To screen a breeding queen
bull To monitor FIP treatment q 8-12 wks
bull To screen blood donor cat
bull To screen prior to FeLV vaccination
Blood fluid Interpretation of FCoV antibody test
I false negative in sick FIP cat
II High titer (gt 11600) in normal cat (esp cat from multi-household) is not indicated FIP
III High titer in fluid high PPV
IV Generally not recommended in sick cat
FCoV antibody in CSF
bull Use of anti-coronavirus antibody testing of cerebrospinal fluid for diagnosis of feline infectious peritonitis involving the central nervous system in cats
bull J Am Vet Med Assoc January 2007230(2)199-205
bull Irene C Boettcher1 Tanja Steinberg Kaspar Matiasek Craig E Greene Katrin Hartmann Andrea Fischer
CSF IgG was detected only in strongly seropositive cats suggested that CSF anti-coronavirus IgG was derived from blood Measurement of
anti-coronavirus IgG in CSF was of equivocal clinical use
Test test test
FCoV RT-PCR test ( bloodeffusion fluidfeces)
Blood FCoV RT-PCR FECV Monocyte-associated viremia Not differentiate FIPV from pathotype
FCoV
Fecal FCoV RT-PC Recommend for house-cat management BUT single positive or negative tests are
meaningless as cats may shed intermittently or may be recently infected
Effusion fluid FCoV RT-PCR bull Generally recommended for fluid bull Positive result high PPV bull But 30 of effusions from cats
with FIP may be negative by RT-PCR
Why false negative 1 FIPV is cell-associated and likely confined to cells of perivascular granuloma (leaking out of pure plasma) 2 Inhibition of RT-PCR by interfering substances in fluid Therefore negative result doesnrsquot exclude FIP
Is FIP a contagious disease (cat-to-cat transmission)
Is FIP a contagious disease (cat-to-cat transmission)
Cats with FIP do not excrete pathogenic FIPV
FECV in enterocytes
Is FIP contagious
Cats with FIP do not appear to be very contagious to cats coming in contact with
Every FIPV isolated from a group outbreak of FIP does NOT genetically identical in its 3c gene mutation
However FIPV is found in the feces of most cats with FIP
Mutation when FECV turns into FIPV
Internal mutation theory bull Genetic changes from FECV
to FIPV
bull Various types of mutation within OPFs 3 and 7
bull 20 of kittens infected with FECV will produce an FIP mutant
Horizontal (cat-to cat) bull Transmission of FIPV
mutants
bull cats with FIP are shedding the same FIPV in their feces
J Gen Virol 2010 Feb91(Pt 2)415-20 doi 101099vir0016485-0 Epub 2009 Nov 4
Feline infectious peritonitis insights into feline coronavirus
pathobiogenesis and epidemiology based on genetic analysis of the viral
3c gene Chang HW1 de Groot RJ Egberink HF Rottier PJ
helliphellipMost cats with FIP had no detectable intestinal feline coronaviruses (FCoVs) and
had seemingly cleared the primary FECV infection In those with detectable intestinal
FCoV the virus always had an intact 3c and seemed to have been acquired by FECV
superinfection Apparently 3c-inactivated viruses replicate not at all--or only poorly--in the
gut explaining the rare incidence of FIP outbreaks
FIP transmission
FIP transmission
bull Vet Res 2013 Jul 174457 doi 1011861297-9716-44-57
bull An outbreak of feline infectious peritonitis in a Taiwanese shelter epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus
bull Wang YT1 Su BL Hsieh LE Chueh LL
bull Abstract
bull helliphellipSequence analysis revealed that the type II FIPV detected from fecal samples body
effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death Taken together our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment
FCoV field strain in FIP cat
Genomic RNA sequence of feline coronavirus strain FCoV C1Je Charlotte Dye BVMampS PhD CertSAM MRCVS
Stuart G Siddell BSc(Hons) PhD
bull This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV) Viral RNAs isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP) derived 100 nucleotide identity
Feline Coronavirus serotypes I and II were reported in natural infection
bull Feline coronavirus serotypes 1 and 2 seroprevalence and association with disease in Switzerland
bull Clin Diagn Lab Immunol October 200512(10)1209-15 bull Maya Kummrow1 Marina L Meli Michael Haessig Enikoe Goenczi Amy Poland Niels C
Pedersen Regina Hofmann-Lehmann Hans Lutz
bull Comparison of serologic techniques for the detection of antibodies against feline coronaviruses
bull J Vet Diagn Invest January 200820(1)45-50 bull Annamaria Pratelli1
bull Prevalence of Korean cats with natural feline coronavirus infections bull Virol J January 20118(0)455 bull Dong-Jun An1 Hye-Young Jeoung Wooseog Jeong Jee Yong Park Myoung-Heon Lee Bong
Kyun Park bull 1National Veterinary Research and Quarantine Service Anyang Kyunggi-do430-824 Korea
bull Moreshellip
Take home message Knowing ME knowing YOU
My team my world
Thank you
Endothelial cells show strongly MHCII antigen positive
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Activated macrophages
Morphologic Features and Development of Granulomatous vasculitis in FIP Kipar et al(2005)
Emigration of FCoV ndashinfected monocytes to vascular perivascular granulomatous infiltrates
with destruction of vascular basal laminar
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Leptomeningeal veins Agglomerate of TNF-α-positive monocytes attached to
venous endothelium Avidin-biotin-peroxidase complex method Papanicolaous hematoxylin counterstain Bar = 10 μm
Objective bullKnowing FCoVs
bullFCoVs in clinical diagnosis
Serology and Molecular diagnosis
Indirect FCoV antibody test Direct (viral load) FCoV RT-PCR
bull Blood
bull Feces
bull Effusion fluid
bull CSF
bull At present NO nucleoprotein sequences unique to pathogenic FCoV (ie not also present in nonpathogenic FCoV) have been identified
FCoV FECV FCoV where are they
Small intestinal enterocytes
Colon -rectum
Healthy shedders
Asymptomatic or mild diarrhea
After clearance from sm intestine FCoVs spread to infect colon and intermittently shedded off
If kittens infected before immune system fully mature levels of FECV replication will be very high
Reinfection may be from FCoV same strains or different strains
Pyogranulomatous inflammation
FIPV infected monocytes perivascular macrophages overproduce neutrophil survival factors Tumor necrosis factor- alpha (TNF ndashalpha) bull Matrix metalloproyeinase-9 bull GM-CSF bull G-CSF Neutrophil survival Development of granuloma lesions
Interpretation of FCoV antibody test
Viral shedding ~ 2 days (FCoV in epithelial cells)
Signs of FIP
bull As early as 2 wk old to 18 months
bull From pyogranulomatous inflammation to clinical signs may be months
From NC Pederson et al (2008) Feline enteric coronavirus infection
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To rule out FIP in sick cats bull effusive FIP
bull non- effusive FIP ( esp cats with GI signs)
bull To screen the FCoV excretors bull Cats in contact with known FCoV shedder
bull Cats in the household
bull New kitten or new cat bringing into the multi-cat household
bull Before receiving immunosuppressive treatment or stressful procedures
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To screen a breeding queen
bull To monitor FIP treatment q 8-12 wks
bull To screen blood donor cat
bull To screen prior to FeLV vaccination
Blood fluid Interpretation of FCoV antibody test
I false negative in sick FIP cat
II High titer (gt 11600) in normal cat (esp cat from multi-household) is not indicated FIP
III High titer in fluid high PPV
IV Generally not recommended in sick cat
FCoV antibody in CSF
bull Use of anti-coronavirus antibody testing of cerebrospinal fluid for diagnosis of feline infectious peritonitis involving the central nervous system in cats
bull J Am Vet Med Assoc January 2007230(2)199-205
bull Irene C Boettcher1 Tanja Steinberg Kaspar Matiasek Craig E Greene Katrin Hartmann Andrea Fischer
CSF IgG was detected only in strongly seropositive cats suggested that CSF anti-coronavirus IgG was derived from blood Measurement of
anti-coronavirus IgG in CSF was of equivocal clinical use
Test test test
FCoV RT-PCR test ( bloodeffusion fluidfeces)
Blood FCoV RT-PCR FECV Monocyte-associated viremia Not differentiate FIPV from pathotype
FCoV
Fecal FCoV RT-PC Recommend for house-cat management BUT single positive or negative tests are
meaningless as cats may shed intermittently or may be recently infected
Effusion fluid FCoV RT-PCR bull Generally recommended for fluid bull Positive result high PPV bull But 30 of effusions from cats
with FIP may be negative by RT-PCR
Why false negative 1 FIPV is cell-associated and likely confined to cells of perivascular granuloma (leaking out of pure plasma) 2 Inhibition of RT-PCR by interfering substances in fluid Therefore negative result doesnrsquot exclude FIP
Is FIP a contagious disease (cat-to-cat transmission)
Is FIP a contagious disease (cat-to-cat transmission)
Cats with FIP do not excrete pathogenic FIPV
FECV in enterocytes
Is FIP contagious
Cats with FIP do not appear to be very contagious to cats coming in contact with
Every FIPV isolated from a group outbreak of FIP does NOT genetically identical in its 3c gene mutation
However FIPV is found in the feces of most cats with FIP
Mutation when FECV turns into FIPV
Internal mutation theory bull Genetic changes from FECV
to FIPV
bull Various types of mutation within OPFs 3 and 7
bull 20 of kittens infected with FECV will produce an FIP mutant
Horizontal (cat-to cat) bull Transmission of FIPV
mutants
bull cats with FIP are shedding the same FIPV in their feces
J Gen Virol 2010 Feb91(Pt 2)415-20 doi 101099vir0016485-0 Epub 2009 Nov 4
Feline infectious peritonitis insights into feline coronavirus
pathobiogenesis and epidemiology based on genetic analysis of the viral
3c gene Chang HW1 de Groot RJ Egberink HF Rottier PJ
helliphellipMost cats with FIP had no detectable intestinal feline coronaviruses (FCoVs) and
had seemingly cleared the primary FECV infection In those with detectable intestinal
FCoV the virus always had an intact 3c and seemed to have been acquired by FECV
superinfection Apparently 3c-inactivated viruses replicate not at all--or only poorly--in the
gut explaining the rare incidence of FIP outbreaks
FIP transmission
FIP transmission
bull Vet Res 2013 Jul 174457 doi 1011861297-9716-44-57
bull An outbreak of feline infectious peritonitis in a Taiwanese shelter epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus
bull Wang YT1 Su BL Hsieh LE Chueh LL
bull Abstract
bull helliphellipSequence analysis revealed that the type II FIPV detected from fecal samples body
effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death Taken together our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment
FCoV field strain in FIP cat
Genomic RNA sequence of feline coronavirus strain FCoV C1Je Charlotte Dye BVMampS PhD CertSAM MRCVS
Stuart G Siddell BSc(Hons) PhD
bull This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV) Viral RNAs isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP) derived 100 nucleotide identity
Feline Coronavirus serotypes I and II were reported in natural infection
bull Feline coronavirus serotypes 1 and 2 seroprevalence and association with disease in Switzerland
bull Clin Diagn Lab Immunol October 200512(10)1209-15 bull Maya Kummrow1 Marina L Meli Michael Haessig Enikoe Goenczi Amy Poland Niels C
Pedersen Regina Hofmann-Lehmann Hans Lutz
bull Comparison of serologic techniques for the detection of antibodies against feline coronaviruses
bull J Vet Diagn Invest January 200820(1)45-50 bull Annamaria Pratelli1
bull Prevalence of Korean cats with natural feline coronavirus infections bull Virol J January 20118(0)455 bull Dong-Jun An1 Hye-Young Jeoung Wooseog Jeong Jee Yong Park Myoung-Heon Lee Bong
Kyun Park bull 1National Veterinary Research and Quarantine Service Anyang Kyunggi-do430-824 Korea
bull Moreshellip
Take home message Knowing ME knowing YOU
My team my world
Thank you
Morphologic Features and Development of Granulomatous vasculitis in FIP Kipar et al(2005)
Emigration of FCoV ndashinfected monocytes to vascular perivascular granulomatous infiltrates
with destruction of vascular basal laminar
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Leptomeningeal veins Agglomerate of TNF-α-positive monocytes attached to
venous endothelium Avidin-biotin-peroxidase complex method Papanicolaous hematoxylin counterstain Bar = 10 μm
Objective bullKnowing FCoVs
bullFCoVs in clinical diagnosis
Serology and Molecular diagnosis
Indirect FCoV antibody test Direct (viral load) FCoV RT-PCR
bull Blood
bull Feces
bull Effusion fluid
bull CSF
bull At present NO nucleoprotein sequences unique to pathogenic FCoV (ie not also present in nonpathogenic FCoV) have been identified
FCoV FECV FCoV where are they
Small intestinal enterocytes
Colon -rectum
Healthy shedders
Asymptomatic or mild diarrhea
After clearance from sm intestine FCoVs spread to infect colon and intermittently shedded off
If kittens infected before immune system fully mature levels of FECV replication will be very high
Reinfection may be from FCoV same strains or different strains
Pyogranulomatous inflammation
FIPV infected monocytes perivascular macrophages overproduce neutrophil survival factors Tumor necrosis factor- alpha (TNF ndashalpha) bull Matrix metalloproyeinase-9 bull GM-CSF bull G-CSF Neutrophil survival Development of granuloma lesions
Interpretation of FCoV antibody test
Viral shedding ~ 2 days (FCoV in epithelial cells)
Signs of FIP
bull As early as 2 wk old to 18 months
bull From pyogranulomatous inflammation to clinical signs may be months
From NC Pederson et al (2008) Feline enteric coronavirus infection
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To rule out FIP in sick cats bull effusive FIP
bull non- effusive FIP ( esp cats with GI signs)
bull To screen the FCoV excretors bull Cats in contact with known FCoV shedder
bull Cats in the household
bull New kitten or new cat bringing into the multi-cat household
bull Before receiving immunosuppressive treatment or stressful procedures
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To screen a breeding queen
bull To monitor FIP treatment q 8-12 wks
bull To screen blood donor cat
bull To screen prior to FeLV vaccination
Blood fluid Interpretation of FCoV antibody test
I false negative in sick FIP cat
II High titer (gt 11600) in normal cat (esp cat from multi-household) is not indicated FIP
III High titer in fluid high PPV
IV Generally not recommended in sick cat
FCoV antibody in CSF
bull Use of anti-coronavirus antibody testing of cerebrospinal fluid for diagnosis of feline infectious peritonitis involving the central nervous system in cats
bull J Am Vet Med Assoc January 2007230(2)199-205
bull Irene C Boettcher1 Tanja Steinberg Kaspar Matiasek Craig E Greene Katrin Hartmann Andrea Fischer
CSF IgG was detected only in strongly seropositive cats suggested that CSF anti-coronavirus IgG was derived from blood Measurement of
anti-coronavirus IgG in CSF was of equivocal clinical use
Test test test
FCoV RT-PCR test ( bloodeffusion fluidfeces)
Blood FCoV RT-PCR FECV Monocyte-associated viremia Not differentiate FIPV from pathotype
FCoV
Fecal FCoV RT-PC Recommend for house-cat management BUT single positive or negative tests are
meaningless as cats may shed intermittently or may be recently infected
Effusion fluid FCoV RT-PCR bull Generally recommended for fluid bull Positive result high PPV bull But 30 of effusions from cats
with FIP may be negative by RT-PCR
Why false negative 1 FIPV is cell-associated and likely confined to cells of perivascular granuloma (leaking out of pure plasma) 2 Inhibition of RT-PCR by interfering substances in fluid Therefore negative result doesnrsquot exclude FIP
Is FIP a contagious disease (cat-to-cat transmission)
Is FIP a contagious disease (cat-to-cat transmission)
Cats with FIP do not excrete pathogenic FIPV
FECV in enterocytes
Is FIP contagious
Cats with FIP do not appear to be very contagious to cats coming in contact with
Every FIPV isolated from a group outbreak of FIP does NOT genetically identical in its 3c gene mutation
However FIPV is found in the feces of most cats with FIP
Mutation when FECV turns into FIPV
Internal mutation theory bull Genetic changes from FECV
to FIPV
bull Various types of mutation within OPFs 3 and 7
bull 20 of kittens infected with FECV will produce an FIP mutant
Horizontal (cat-to cat) bull Transmission of FIPV
mutants
bull cats with FIP are shedding the same FIPV in their feces
J Gen Virol 2010 Feb91(Pt 2)415-20 doi 101099vir0016485-0 Epub 2009 Nov 4
Feline infectious peritonitis insights into feline coronavirus
pathobiogenesis and epidemiology based on genetic analysis of the viral
3c gene Chang HW1 de Groot RJ Egberink HF Rottier PJ
helliphellipMost cats with FIP had no detectable intestinal feline coronaviruses (FCoVs) and
had seemingly cleared the primary FECV infection In those with detectable intestinal
FCoV the virus always had an intact 3c and seemed to have been acquired by FECV
superinfection Apparently 3c-inactivated viruses replicate not at all--or only poorly--in the
gut explaining the rare incidence of FIP outbreaks
FIP transmission
FIP transmission
bull Vet Res 2013 Jul 174457 doi 1011861297-9716-44-57
bull An outbreak of feline infectious peritonitis in a Taiwanese shelter epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus
bull Wang YT1 Su BL Hsieh LE Chueh LL
bull Abstract
bull helliphellipSequence analysis revealed that the type II FIPV detected from fecal samples body
effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death Taken together our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment
FCoV field strain in FIP cat
Genomic RNA sequence of feline coronavirus strain FCoV C1Je Charlotte Dye BVMampS PhD CertSAM MRCVS
Stuart G Siddell BSc(Hons) PhD
bull This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV) Viral RNAs isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP) derived 100 nucleotide identity
Feline Coronavirus serotypes I and II were reported in natural infection
bull Feline coronavirus serotypes 1 and 2 seroprevalence and association with disease in Switzerland
bull Clin Diagn Lab Immunol October 200512(10)1209-15 bull Maya Kummrow1 Marina L Meli Michael Haessig Enikoe Goenczi Amy Poland Niels C
Pedersen Regina Hofmann-Lehmann Hans Lutz
bull Comparison of serologic techniques for the detection of antibodies against feline coronaviruses
bull J Vet Diagn Invest January 200820(1)45-50 bull Annamaria Pratelli1
bull Prevalence of Korean cats with natural feline coronavirus infections bull Virol J January 20118(0)455 bull Dong-Jun An1 Hye-Young Jeoung Wooseog Jeong Jee Yong Park Myoung-Heon Lee Bong
Kyun Park bull 1National Veterinary Research and Quarantine Service Anyang Kyunggi-do430-824 Korea
bull Moreshellip
Take home message Knowing ME knowing YOU
My team my world
Thank you
Emigration of FCoV ndashinfected monocytes to vascular perivascular granulomatous infiltrates
with destruction of vascular basal laminar
A Kipar et al Vet Pathol 200542321-330
Copyright copy by American College of Veterinary Pathologists
Leptomeningeal veins Agglomerate of TNF-α-positive monocytes attached to
venous endothelium Avidin-biotin-peroxidase complex method Papanicolaous hematoxylin counterstain Bar = 10 μm
Objective bullKnowing FCoVs
bullFCoVs in clinical diagnosis
Serology and Molecular diagnosis
Indirect FCoV antibody test Direct (viral load) FCoV RT-PCR
bull Blood
bull Feces
bull Effusion fluid
bull CSF
bull At present NO nucleoprotein sequences unique to pathogenic FCoV (ie not also present in nonpathogenic FCoV) have been identified
FCoV FECV FCoV where are they
Small intestinal enterocytes
Colon -rectum
Healthy shedders
Asymptomatic or mild diarrhea
After clearance from sm intestine FCoVs spread to infect colon and intermittently shedded off
If kittens infected before immune system fully mature levels of FECV replication will be very high
Reinfection may be from FCoV same strains or different strains
Pyogranulomatous inflammation
FIPV infected monocytes perivascular macrophages overproduce neutrophil survival factors Tumor necrosis factor- alpha (TNF ndashalpha) bull Matrix metalloproyeinase-9 bull GM-CSF bull G-CSF Neutrophil survival Development of granuloma lesions
Interpretation of FCoV antibody test
Viral shedding ~ 2 days (FCoV in epithelial cells)
Signs of FIP
bull As early as 2 wk old to 18 months
bull From pyogranulomatous inflammation to clinical signs may be months
From NC Pederson et al (2008) Feline enteric coronavirus infection
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To rule out FIP in sick cats bull effusive FIP
bull non- effusive FIP ( esp cats with GI signs)
bull To screen the FCoV excretors bull Cats in contact with known FCoV shedder
bull Cats in the household
bull New kitten or new cat bringing into the multi-cat household
bull Before receiving immunosuppressive treatment or stressful procedures
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To screen a breeding queen
bull To monitor FIP treatment q 8-12 wks
bull To screen blood donor cat
bull To screen prior to FeLV vaccination
Blood fluid Interpretation of FCoV antibody test
I false negative in sick FIP cat
II High titer (gt 11600) in normal cat (esp cat from multi-household) is not indicated FIP
III High titer in fluid high PPV
IV Generally not recommended in sick cat
FCoV antibody in CSF
bull Use of anti-coronavirus antibody testing of cerebrospinal fluid for diagnosis of feline infectious peritonitis involving the central nervous system in cats
bull J Am Vet Med Assoc January 2007230(2)199-205
bull Irene C Boettcher1 Tanja Steinberg Kaspar Matiasek Craig E Greene Katrin Hartmann Andrea Fischer
CSF IgG was detected only in strongly seropositive cats suggested that CSF anti-coronavirus IgG was derived from blood Measurement of
anti-coronavirus IgG in CSF was of equivocal clinical use
Test test test
FCoV RT-PCR test ( bloodeffusion fluidfeces)
Blood FCoV RT-PCR FECV Monocyte-associated viremia Not differentiate FIPV from pathotype
FCoV
Fecal FCoV RT-PC Recommend for house-cat management BUT single positive or negative tests are
meaningless as cats may shed intermittently or may be recently infected
Effusion fluid FCoV RT-PCR bull Generally recommended for fluid bull Positive result high PPV bull But 30 of effusions from cats
with FIP may be negative by RT-PCR
Why false negative 1 FIPV is cell-associated and likely confined to cells of perivascular granuloma (leaking out of pure plasma) 2 Inhibition of RT-PCR by interfering substances in fluid Therefore negative result doesnrsquot exclude FIP
Is FIP a contagious disease (cat-to-cat transmission)
Is FIP a contagious disease (cat-to-cat transmission)
Cats with FIP do not excrete pathogenic FIPV
FECV in enterocytes
Is FIP contagious
Cats with FIP do not appear to be very contagious to cats coming in contact with
Every FIPV isolated from a group outbreak of FIP does NOT genetically identical in its 3c gene mutation
However FIPV is found in the feces of most cats with FIP
Mutation when FECV turns into FIPV
Internal mutation theory bull Genetic changes from FECV
to FIPV
bull Various types of mutation within OPFs 3 and 7
bull 20 of kittens infected with FECV will produce an FIP mutant
Horizontal (cat-to cat) bull Transmission of FIPV
mutants
bull cats with FIP are shedding the same FIPV in their feces
J Gen Virol 2010 Feb91(Pt 2)415-20 doi 101099vir0016485-0 Epub 2009 Nov 4
Feline infectious peritonitis insights into feline coronavirus
pathobiogenesis and epidemiology based on genetic analysis of the viral
3c gene Chang HW1 de Groot RJ Egberink HF Rottier PJ
helliphellipMost cats with FIP had no detectable intestinal feline coronaviruses (FCoVs) and
had seemingly cleared the primary FECV infection In those with detectable intestinal
FCoV the virus always had an intact 3c and seemed to have been acquired by FECV
superinfection Apparently 3c-inactivated viruses replicate not at all--or only poorly--in the
gut explaining the rare incidence of FIP outbreaks
FIP transmission
FIP transmission
bull Vet Res 2013 Jul 174457 doi 1011861297-9716-44-57
bull An outbreak of feline infectious peritonitis in a Taiwanese shelter epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus
bull Wang YT1 Su BL Hsieh LE Chueh LL
bull Abstract
bull helliphellipSequence analysis revealed that the type II FIPV detected from fecal samples body
effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death Taken together our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment
FCoV field strain in FIP cat
Genomic RNA sequence of feline coronavirus strain FCoV C1Je Charlotte Dye BVMampS PhD CertSAM MRCVS
Stuart G Siddell BSc(Hons) PhD
bull This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV) Viral RNAs isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP) derived 100 nucleotide identity
Feline Coronavirus serotypes I and II were reported in natural infection
bull Feline coronavirus serotypes 1 and 2 seroprevalence and association with disease in Switzerland
bull Clin Diagn Lab Immunol October 200512(10)1209-15 bull Maya Kummrow1 Marina L Meli Michael Haessig Enikoe Goenczi Amy Poland Niels C
Pedersen Regina Hofmann-Lehmann Hans Lutz
bull Comparison of serologic techniques for the detection of antibodies against feline coronaviruses
bull J Vet Diagn Invest January 200820(1)45-50 bull Annamaria Pratelli1
bull Prevalence of Korean cats with natural feline coronavirus infections bull Virol J January 20118(0)455 bull Dong-Jun An1 Hye-Young Jeoung Wooseog Jeong Jee Yong Park Myoung-Heon Lee Bong
Kyun Park bull 1National Veterinary Research and Quarantine Service Anyang Kyunggi-do430-824 Korea
bull Moreshellip
Take home message Knowing ME knowing YOU
My team my world
Thank you
Objective bullKnowing FCoVs
bullFCoVs in clinical diagnosis
Serology and Molecular diagnosis
Indirect FCoV antibody test Direct (viral load) FCoV RT-PCR
bull Blood
bull Feces
bull Effusion fluid
bull CSF
bull At present NO nucleoprotein sequences unique to pathogenic FCoV (ie not also present in nonpathogenic FCoV) have been identified
FCoV FECV FCoV where are they
Small intestinal enterocytes
Colon -rectum
Healthy shedders
Asymptomatic or mild diarrhea
After clearance from sm intestine FCoVs spread to infect colon and intermittently shedded off
If kittens infected before immune system fully mature levels of FECV replication will be very high
Reinfection may be from FCoV same strains or different strains
Pyogranulomatous inflammation
FIPV infected monocytes perivascular macrophages overproduce neutrophil survival factors Tumor necrosis factor- alpha (TNF ndashalpha) bull Matrix metalloproyeinase-9 bull GM-CSF bull G-CSF Neutrophil survival Development of granuloma lesions
Interpretation of FCoV antibody test
Viral shedding ~ 2 days (FCoV in epithelial cells)
Signs of FIP
bull As early as 2 wk old to 18 months
bull From pyogranulomatous inflammation to clinical signs may be months
From NC Pederson et al (2008) Feline enteric coronavirus infection
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To rule out FIP in sick cats bull effusive FIP
bull non- effusive FIP ( esp cats with GI signs)
bull To screen the FCoV excretors bull Cats in contact with known FCoV shedder
bull Cats in the household
bull New kitten or new cat bringing into the multi-cat household
bull Before receiving immunosuppressive treatment or stressful procedures
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To screen a breeding queen
bull To monitor FIP treatment q 8-12 wks
bull To screen blood donor cat
bull To screen prior to FeLV vaccination
Blood fluid Interpretation of FCoV antibody test
I false negative in sick FIP cat
II High titer (gt 11600) in normal cat (esp cat from multi-household) is not indicated FIP
III High titer in fluid high PPV
IV Generally not recommended in sick cat
FCoV antibody in CSF
bull Use of anti-coronavirus antibody testing of cerebrospinal fluid for diagnosis of feline infectious peritonitis involving the central nervous system in cats
bull J Am Vet Med Assoc January 2007230(2)199-205
bull Irene C Boettcher1 Tanja Steinberg Kaspar Matiasek Craig E Greene Katrin Hartmann Andrea Fischer
CSF IgG was detected only in strongly seropositive cats suggested that CSF anti-coronavirus IgG was derived from blood Measurement of
anti-coronavirus IgG in CSF was of equivocal clinical use
Test test test
FCoV RT-PCR test ( bloodeffusion fluidfeces)
Blood FCoV RT-PCR FECV Monocyte-associated viremia Not differentiate FIPV from pathotype
FCoV
Fecal FCoV RT-PC Recommend for house-cat management BUT single positive or negative tests are
meaningless as cats may shed intermittently or may be recently infected
Effusion fluid FCoV RT-PCR bull Generally recommended for fluid bull Positive result high PPV bull But 30 of effusions from cats
with FIP may be negative by RT-PCR
Why false negative 1 FIPV is cell-associated and likely confined to cells of perivascular granuloma (leaking out of pure plasma) 2 Inhibition of RT-PCR by interfering substances in fluid Therefore negative result doesnrsquot exclude FIP
Is FIP a contagious disease (cat-to-cat transmission)
Is FIP a contagious disease (cat-to-cat transmission)
Cats with FIP do not excrete pathogenic FIPV
FECV in enterocytes
Is FIP contagious
Cats with FIP do not appear to be very contagious to cats coming in contact with
Every FIPV isolated from a group outbreak of FIP does NOT genetically identical in its 3c gene mutation
However FIPV is found in the feces of most cats with FIP
Mutation when FECV turns into FIPV
Internal mutation theory bull Genetic changes from FECV
to FIPV
bull Various types of mutation within OPFs 3 and 7
bull 20 of kittens infected with FECV will produce an FIP mutant
Horizontal (cat-to cat) bull Transmission of FIPV
mutants
bull cats with FIP are shedding the same FIPV in their feces
J Gen Virol 2010 Feb91(Pt 2)415-20 doi 101099vir0016485-0 Epub 2009 Nov 4
Feline infectious peritonitis insights into feline coronavirus
pathobiogenesis and epidemiology based on genetic analysis of the viral
3c gene Chang HW1 de Groot RJ Egberink HF Rottier PJ
helliphellipMost cats with FIP had no detectable intestinal feline coronaviruses (FCoVs) and
had seemingly cleared the primary FECV infection In those with detectable intestinal
FCoV the virus always had an intact 3c and seemed to have been acquired by FECV
superinfection Apparently 3c-inactivated viruses replicate not at all--or only poorly--in the
gut explaining the rare incidence of FIP outbreaks
FIP transmission
FIP transmission
bull Vet Res 2013 Jul 174457 doi 1011861297-9716-44-57
bull An outbreak of feline infectious peritonitis in a Taiwanese shelter epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus
bull Wang YT1 Su BL Hsieh LE Chueh LL
bull Abstract
bull helliphellipSequence analysis revealed that the type II FIPV detected from fecal samples body
effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death Taken together our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment
FCoV field strain in FIP cat
Genomic RNA sequence of feline coronavirus strain FCoV C1Je Charlotte Dye BVMampS PhD CertSAM MRCVS
Stuart G Siddell BSc(Hons) PhD
bull This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV) Viral RNAs isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP) derived 100 nucleotide identity
Feline Coronavirus serotypes I and II were reported in natural infection
bull Feline coronavirus serotypes 1 and 2 seroprevalence and association with disease in Switzerland
bull Clin Diagn Lab Immunol October 200512(10)1209-15 bull Maya Kummrow1 Marina L Meli Michael Haessig Enikoe Goenczi Amy Poland Niels C
Pedersen Regina Hofmann-Lehmann Hans Lutz
bull Comparison of serologic techniques for the detection of antibodies against feline coronaviruses
bull J Vet Diagn Invest January 200820(1)45-50 bull Annamaria Pratelli1
bull Prevalence of Korean cats with natural feline coronavirus infections bull Virol J January 20118(0)455 bull Dong-Jun An1 Hye-Young Jeoung Wooseog Jeong Jee Yong Park Myoung-Heon Lee Bong
Kyun Park bull 1National Veterinary Research and Quarantine Service Anyang Kyunggi-do430-824 Korea
bull Moreshellip
Take home message Knowing ME knowing YOU
My team my world
Thank you
Serology and Molecular diagnosis
Indirect FCoV antibody test Direct (viral load) FCoV RT-PCR
bull Blood
bull Feces
bull Effusion fluid
bull CSF
bull At present NO nucleoprotein sequences unique to pathogenic FCoV (ie not also present in nonpathogenic FCoV) have been identified
FCoV FECV FCoV where are they
Small intestinal enterocytes
Colon -rectum
Healthy shedders
Asymptomatic or mild diarrhea
After clearance from sm intestine FCoVs spread to infect colon and intermittently shedded off
If kittens infected before immune system fully mature levels of FECV replication will be very high
Reinfection may be from FCoV same strains or different strains
Pyogranulomatous inflammation
FIPV infected monocytes perivascular macrophages overproduce neutrophil survival factors Tumor necrosis factor- alpha (TNF ndashalpha) bull Matrix metalloproyeinase-9 bull GM-CSF bull G-CSF Neutrophil survival Development of granuloma lesions
Interpretation of FCoV antibody test
Viral shedding ~ 2 days (FCoV in epithelial cells)
Signs of FIP
bull As early as 2 wk old to 18 months
bull From pyogranulomatous inflammation to clinical signs may be months
From NC Pederson et al (2008) Feline enteric coronavirus infection
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To rule out FIP in sick cats bull effusive FIP
bull non- effusive FIP ( esp cats with GI signs)
bull To screen the FCoV excretors bull Cats in contact with known FCoV shedder
bull Cats in the household
bull New kitten or new cat bringing into the multi-cat household
bull Before receiving immunosuppressive treatment or stressful procedures
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To screen a breeding queen
bull To monitor FIP treatment q 8-12 wks
bull To screen blood donor cat
bull To screen prior to FeLV vaccination
Blood fluid Interpretation of FCoV antibody test
I false negative in sick FIP cat
II High titer (gt 11600) in normal cat (esp cat from multi-household) is not indicated FIP
III High titer in fluid high PPV
IV Generally not recommended in sick cat
FCoV antibody in CSF
bull Use of anti-coronavirus antibody testing of cerebrospinal fluid for diagnosis of feline infectious peritonitis involving the central nervous system in cats
bull J Am Vet Med Assoc January 2007230(2)199-205
bull Irene C Boettcher1 Tanja Steinberg Kaspar Matiasek Craig E Greene Katrin Hartmann Andrea Fischer
CSF IgG was detected only in strongly seropositive cats suggested that CSF anti-coronavirus IgG was derived from blood Measurement of
anti-coronavirus IgG in CSF was of equivocal clinical use
Test test test
FCoV RT-PCR test ( bloodeffusion fluidfeces)
Blood FCoV RT-PCR FECV Monocyte-associated viremia Not differentiate FIPV from pathotype
FCoV
Fecal FCoV RT-PC Recommend for house-cat management BUT single positive or negative tests are
meaningless as cats may shed intermittently or may be recently infected
Effusion fluid FCoV RT-PCR bull Generally recommended for fluid bull Positive result high PPV bull But 30 of effusions from cats
with FIP may be negative by RT-PCR
Why false negative 1 FIPV is cell-associated and likely confined to cells of perivascular granuloma (leaking out of pure plasma) 2 Inhibition of RT-PCR by interfering substances in fluid Therefore negative result doesnrsquot exclude FIP
Is FIP a contagious disease (cat-to-cat transmission)
Is FIP a contagious disease (cat-to-cat transmission)
Cats with FIP do not excrete pathogenic FIPV
FECV in enterocytes
Is FIP contagious
Cats with FIP do not appear to be very contagious to cats coming in contact with
Every FIPV isolated from a group outbreak of FIP does NOT genetically identical in its 3c gene mutation
However FIPV is found in the feces of most cats with FIP
Mutation when FECV turns into FIPV
Internal mutation theory bull Genetic changes from FECV
to FIPV
bull Various types of mutation within OPFs 3 and 7
bull 20 of kittens infected with FECV will produce an FIP mutant
Horizontal (cat-to cat) bull Transmission of FIPV
mutants
bull cats with FIP are shedding the same FIPV in their feces
J Gen Virol 2010 Feb91(Pt 2)415-20 doi 101099vir0016485-0 Epub 2009 Nov 4
Feline infectious peritonitis insights into feline coronavirus
pathobiogenesis and epidemiology based on genetic analysis of the viral
3c gene Chang HW1 de Groot RJ Egberink HF Rottier PJ
helliphellipMost cats with FIP had no detectable intestinal feline coronaviruses (FCoVs) and
had seemingly cleared the primary FECV infection In those with detectable intestinal
FCoV the virus always had an intact 3c and seemed to have been acquired by FECV
superinfection Apparently 3c-inactivated viruses replicate not at all--or only poorly--in the
gut explaining the rare incidence of FIP outbreaks
FIP transmission
FIP transmission
bull Vet Res 2013 Jul 174457 doi 1011861297-9716-44-57
bull An outbreak of feline infectious peritonitis in a Taiwanese shelter epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus
bull Wang YT1 Su BL Hsieh LE Chueh LL
bull Abstract
bull helliphellipSequence analysis revealed that the type II FIPV detected from fecal samples body
effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death Taken together our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment
FCoV field strain in FIP cat
Genomic RNA sequence of feline coronavirus strain FCoV C1Je Charlotte Dye BVMampS PhD CertSAM MRCVS
Stuart G Siddell BSc(Hons) PhD
bull This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV) Viral RNAs isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP) derived 100 nucleotide identity
Feline Coronavirus serotypes I and II were reported in natural infection
bull Feline coronavirus serotypes 1 and 2 seroprevalence and association with disease in Switzerland
bull Clin Diagn Lab Immunol October 200512(10)1209-15 bull Maya Kummrow1 Marina L Meli Michael Haessig Enikoe Goenczi Amy Poland Niels C
Pedersen Regina Hofmann-Lehmann Hans Lutz
bull Comparison of serologic techniques for the detection of antibodies against feline coronaviruses
bull J Vet Diagn Invest January 200820(1)45-50 bull Annamaria Pratelli1
bull Prevalence of Korean cats with natural feline coronavirus infections bull Virol J January 20118(0)455 bull Dong-Jun An1 Hye-Young Jeoung Wooseog Jeong Jee Yong Park Myoung-Heon Lee Bong
Kyun Park bull 1National Veterinary Research and Quarantine Service Anyang Kyunggi-do430-824 Korea
bull Moreshellip
Take home message Knowing ME knowing YOU
My team my world
Thank you
FCoV FECV FCoV where are they
Small intestinal enterocytes
Colon -rectum
Healthy shedders
Asymptomatic or mild diarrhea
After clearance from sm intestine FCoVs spread to infect colon and intermittently shedded off
If kittens infected before immune system fully mature levels of FECV replication will be very high
Reinfection may be from FCoV same strains or different strains
Pyogranulomatous inflammation
FIPV infected monocytes perivascular macrophages overproduce neutrophil survival factors Tumor necrosis factor- alpha (TNF ndashalpha) bull Matrix metalloproyeinase-9 bull GM-CSF bull G-CSF Neutrophil survival Development of granuloma lesions
Interpretation of FCoV antibody test
Viral shedding ~ 2 days (FCoV in epithelial cells)
Signs of FIP
bull As early as 2 wk old to 18 months
bull From pyogranulomatous inflammation to clinical signs may be months
From NC Pederson et al (2008) Feline enteric coronavirus infection
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To rule out FIP in sick cats bull effusive FIP
bull non- effusive FIP ( esp cats with GI signs)
bull To screen the FCoV excretors bull Cats in contact with known FCoV shedder
bull Cats in the household
bull New kitten or new cat bringing into the multi-cat household
bull Before receiving immunosuppressive treatment or stressful procedures
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To screen a breeding queen
bull To monitor FIP treatment q 8-12 wks
bull To screen blood donor cat
bull To screen prior to FeLV vaccination
Blood fluid Interpretation of FCoV antibody test
I false negative in sick FIP cat
II High titer (gt 11600) in normal cat (esp cat from multi-household) is not indicated FIP
III High titer in fluid high PPV
IV Generally not recommended in sick cat
FCoV antibody in CSF
bull Use of anti-coronavirus antibody testing of cerebrospinal fluid for diagnosis of feline infectious peritonitis involving the central nervous system in cats
bull J Am Vet Med Assoc January 2007230(2)199-205
bull Irene C Boettcher1 Tanja Steinberg Kaspar Matiasek Craig E Greene Katrin Hartmann Andrea Fischer
CSF IgG was detected only in strongly seropositive cats suggested that CSF anti-coronavirus IgG was derived from blood Measurement of
anti-coronavirus IgG in CSF was of equivocal clinical use
Test test test
FCoV RT-PCR test ( bloodeffusion fluidfeces)
Blood FCoV RT-PCR FECV Monocyte-associated viremia Not differentiate FIPV from pathotype
FCoV
Fecal FCoV RT-PC Recommend for house-cat management BUT single positive or negative tests are
meaningless as cats may shed intermittently or may be recently infected
Effusion fluid FCoV RT-PCR bull Generally recommended for fluid bull Positive result high PPV bull But 30 of effusions from cats
with FIP may be negative by RT-PCR
Why false negative 1 FIPV is cell-associated and likely confined to cells of perivascular granuloma (leaking out of pure plasma) 2 Inhibition of RT-PCR by interfering substances in fluid Therefore negative result doesnrsquot exclude FIP
Is FIP a contagious disease (cat-to-cat transmission)
Is FIP a contagious disease (cat-to-cat transmission)
Cats with FIP do not excrete pathogenic FIPV
FECV in enterocytes
Is FIP contagious
Cats with FIP do not appear to be very contagious to cats coming in contact with
Every FIPV isolated from a group outbreak of FIP does NOT genetically identical in its 3c gene mutation
However FIPV is found in the feces of most cats with FIP
Mutation when FECV turns into FIPV
Internal mutation theory bull Genetic changes from FECV
to FIPV
bull Various types of mutation within OPFs 3 and 7
bull 20 of kittens infected with FECV will produce an FIP mutant
Horizontal (cat-to cat) bull Transmission of FIPV
mutants
bull cats with FIP are shedding the same FIPV in their feces
J Gen Virol 2010 Feb91(Pt 2)415-20 doi 101099vir0016485-0 Epub 2009 Nov 4
Feline infectious peritonitis insights into feline coronavirus
pathobiogenesis and epidemiology based on genetic analysis of the viral
3c gene Chang HW1 de Groot RJ Egberink HF Rottier PJ
helliphellipMost cats with FIP had no detectable intestinal feline coronaviruses (FCoVs) and
had seemingly cleared the primary FECV infection In those with detectable intestinal
FCoV the virus always had an intact 3c and seemed to have been acquired by FECV
superinfection Apparently 3c-inactivated viruses replicate not at all--or only poorly--in the
gut explaining the rare incidence of FIP outbreaks
FIP transmission
FIP transmission
bull Vet Res 2013 Jul 174457 doi 1011861297-9716-44-57
bull An outbreak of feline infectious peritonitis in a Taiwanese shelter epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus
bull Wang YT1 Su BL Hsieh LE Chueh LL
bull Abstract
bull helliphellipSequence analysis revealed that the type II FIPV detected from fecal samples body
effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death Taken together our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment
FCoV field strain in FIP cat
Genomic RNA sequence of feline coronavirus strain FCoV C1Je Charlotte Dye BVMampS PhD CertSAM MRCVS
Stuart G Siddell BSc(Hons) PhD
bull This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV) Viral RNAs isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP) derived 100 nucleotide identity
Feline Coronavirus serotypes I and II were reported in natural infection
bull Feline coronavirus serotypes 1 and 2 seroprevalence and association with disease in Switzerland
bull Clin Diagn Lab Immunol October 200512(10)1209-15 bull Maya Kummrow1 Marina L Meli Michael Haessig Enikoe Goenczi Amy Poland Niels C
Pedersen Regina Hofmann-Lehmann Hans Lutz
bull Comparison of serologic techniques for the detection of antibodies against feline coronaviruses
bull J Vet Diagn Invest January 200820(1)45-50 bull Annamaria Pratelli1
bull Prevalence of Korean cats with natural feline coronavirus infections bull Virol J January 20118(0)455 bull Dong-Jun An1 Hye-Young Jeoung Wooseog Jeong Jee Yong Park Myoung-Heon Lee Bong
Kyun Park bull 1National Veterinary Research and Quarantine Service Anyang Kyunggi-do430-824 Korea
bull Moreshellip
Take home message Knowing ME knowing YOU
My team my world
Thank you
If kittens infected before immune system fully mature levels of FECV replication will be very high
Reinfection may be from FCoV same strains or different strains
Pyogranulomatous inflammation
FIPV infected monocytes perivascular macrophages overproduce neutrophil survival factors Tumor necrosis factor- alpha (TNF ndashalpha) bull Matrix metalloproyeinase-9 bull GM-CSF bull G-CSF Neutrophil survival Development of granuloma lesions
Interpretation of FCoV antibody test
Viral shedding ~ 2 days (FCoV in epithelial cells)
Signs of FIP
bull As early as 2 wk old to 18 months
bull From pyogranulomatous inflammation to clinical signs may be months
From NC Pederson et al (2008) Feline enteric coronavirus infection
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To rule out FIP in sick cats bull effusive FIP
bull non- effusive FIP ( esp cats with GI signs)
bull To screen the FCoV excretors bull Cats in contact with known FCoV shedder
bull Cats in the household
bull New kitten or new cat bringing into the multi-cat household
bull Before receiving immunosuppressive treatment or stressful procedures
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To screen a breeding queen
bull To monitor FIP treatment q 8-12 wks
bull To screen blood donor cat
bull To screen prior to FeLV vaccination
Blood fluid Interpretation of FCoV antibody test
I false negative in sick FIP cat
II High titer (gt 11600) in normal cat (esp cat from multi-household) is not indicated FIP
III High titer in fluid high PPV
IV Generally not recommended in sick cat
FCoV antibody in CSF
bull Use of anti-coronavirus antibody testing of cerebrospinal fluid for diagnosis of feline infectious peritonitis involving the central nervous system in cats
bull J Am Vet Med Assoc January 2007230(2)199-205
bull Irene C Boettcher1 Tanja Steinberg Kaspar Matiasek Craig E Greene Katrin Hartmann Andrea Fischer
CSF IgG was detected only in strongly seropositive cats suggested that CSF anti-coronavirus IgG was derived from blood Measurement of
anti-coronavirus IgG in CSF was of equivocal clinical use
Test test test
FCoV RT-PCR test ( bloodeffusion fluidfeces)
Blood FCoV RT-PCR FECV Monocyte-associated viremia Not differentiate FIPV from pathotype
FCoV
Fecal FCoV RT-PC Recommend for house-cat management BUT single positive or negative tests are
meaningless as cats may shed intermittently or may be recently infected
Effusion fluid FCoV RT-PCR bull Generally recommended for fluid bull Positive result high PPV bull But 30 of effusions from cats
with FIP may be negative by RT-PCR
Why false negative 1 FIPV is cell-associated and likely confined to cells of perivascular granuloma (leaking out of pure plasma) 2 Inhibition of RT-PCR by interfering substances in fluid Therefore negative result doesnrsquot exclude FIP
Is FIP a contagious disease (cat-to-cat transmission)
Is FIP a contagious disease (cat-to-cat transmission)
Cats with FIP do not excrete pathogenic FIPV
FECV in enterocytes
Is FIP contagious
Cats with FIP do not appear to be very contagious to cats coming in contact with
Every FIPV isolated from a group outbreak of FIP does NOT genetically identical in its 3c gene mutation
However FIPV is found in the feces of most cats with FIP
Mutation when FECV turns into FIPV
Internal mutation theory bull Genetic changes from FECV
to FIPV
bull Various types of mutation within OPFs 3 and 7
bull 20 of kittens infected with FECV will produce an FIP mutant
Horizontal (cat-to cat) bull Transmission of FIPV
mutants
bull cats with FIP are shedding the same FIPV in their feces
J Gen Virol 2010 Feb91(Pt 2)415-20 doi 101099vir0016485-0 Epub 2009 Nov 4
Feline infectious peritonitis insights into feline coronavirus
pathobiogenesis and epidemiology based on genetic analysis of the viral
3c gene Chang HW1 de Groot RJ Egberink HF Rottier PJ
helliphellipMost cats with FIP had no detectable intestinal feline coronaviruses (FCoVs) and
had seemingly cleared the primary FECV infection In those with detectable intestinal
FCoV the virus always had an intact 3c and seemed to have been acquired by FECV
superinfection Apparently 3c-inactivated viruses replicate not at all--or only poorly--in the
gut explaining the rare incidence of FIP outbreaks
FIP transmission
FIP transmission
bull Vet Res 2013 Jul 174457 doi 1011861297-9716-44-57
bull An outbreak of feline infectious peritonitis in a Taiwanese shelter epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus
bull Wang YT1 Su BL Hsieh LE Chueh LL
bull Abstract
bull helliphellipSequence analysis revealed that the type II FIPV detected from fecal samples body
effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death Taken together our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment
FCoV field strain in FIP cat
Genomic RNA sequence of feline coronavirus strain FCoV C1Je Charlotte Dye BVMampS PhD CertSAM MRCVS
Stuart G Siddell BSc(Hons) PhD
bull This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV) Viral RNAs isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP) derived 100 nucleotide identity
Feline Coronavirus serotypes I and II were reported in natural infection
bull Feline coronavirus serotypes 1 and 2 seroprevalence and association with disease in Switzerland
bull Clin Diagn Lab Immunol October 200512(10)1209-15 bull Maya Kummrow1 Marina L Meli Michael Haessig Enikoe Goenczi Amy Poland Niels C
Pedersen Regina Hofmann-Lehmann Hans Lutz
bull Comparison of serologic techniques for the detection of antibodies against feline coronaviruses
bull J Vet Diagn Invest January 200820(1)45-50 bull Annamaria Pratelli1
bull Prevalence of Korean cats with natural feline coronavirus infections bull Virol J January 20118(0)455 bull Dong-Jun An1 Hye-Young Jeoung Wooseog Jeong Jee Yong Park Myoung-Heon Lee Bong
Kyun Park bull 1National Veterinary Research and Quarantine Service Anyang Kyunggi-do430-824 Korea
bull Moreshellip
Take home message Knowing ME knowing YOU
My team my world
Thank you
Reinfection may be from FCoV same strains or different strains
Pyogranulomatous inflammation
FIPV infected monocytes perivascular macrophages overproduce neutrophil survival factors Tumor necrosis factor- alpha (TNF ndashalpha) bull Matrix metalloproyeinase-9 bull GM-CSF bull G-CSF Neutrophil survival Development of granuloma lesions
Interpretation of FCoV antibody test
Viral shedding ~ 2 days (FCoV in epithelial cells)
Signs of FIP
bull As early as 2 wk old to 18 months
bull From pyogranulomatous inflammation to clinical signs may be months
From NC Pederson et al (2008) Feline enteric coronavirus infection
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To rule out FIP in sick cats bull effusive FIP
bull non- effusive FIP ( esp cats with GI signs)
bull To screen the FCoV excretors bull Cats in contact with known FCoV shedder
bull Cats in the household
bull New kitten or new cat bringing into the multi-cat household
bull Before receiving immunosuppressive treatment or stressful procedures
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To screen a breeding queen
bull To monitor FIP treatment q 8-12 wks
bull To screen blood donor cat
bull To screen prior to FeLV vaccination
Blood fluid Interpretation of FCoV antibody test
I false negative in sick FIP cat
II High titer (gt 11600) in normal cat (esp cat from multi-household) is not indicated FIP
III High titer in fluid high PPV
IV Generally not recommended in sick cat
FCoV antibody in CSF
bull Use of anti-coronavirus antibody testing of cerebrospinal fluid for diagnosis of feline infectious peritonitis involving the central nervous system in cats
bull J Am Vet Med Assoc January 2007230(2)199-205
bull Irene C Boettcher1 Tanja Steinberg Kaspar Matiasek Craig E Greene Katrin Hartmann Andrea Fischer
CSF IgG was detected only in strongly seropositive cats suggested that CSF anti-coronavirus IgG was derived from blood Measurement of
anti-coronavirus IgG in CSF was of equivocal clinical use
Test test test
FCoV RT-PCR test ( bloodeffusion fluidfeces)
Blood FCoV RT-PCR FECV Monocyte-associated viremia Not differentiate FIPV from pathotype
FCoV
Fecal FCoV RT-PC Recommend for house-cat management BUT single positive or negative tests are
meaningless as cats may shed intermittently or may be recently infected
Effusion fluid FCoV RT-PCR bull Generally recommended for fluid bull Positive result high PPV bull But 30 of effusions from cats
with FIP may be negative by RT-PCR
Why false negative 1 FIPV is cell-associated and likely confined to cells of perivascular granuloma (leaking out of pure plasma) 2 Inhibition of RT-PCR by interfering substances in fluid Therefore negative result doesnrsquot exclude FIP
Is FIP a contagious disease (cat-to-cat transmission)
Is FIP a contagious disease (cat-to-cat transmission)
Cats with FIP do not excrete pathogenic FIPV
FECV in enterocytes
Is FIP contagious
Cats with FIP do not appear to be very contagious to cats coming in contact with
Every FIPV isolated from a group outbreak of FIP does NOT genetically identical in its 3c gene mutation
However FIPV is found in the feces of most cats with FIP
Mutation when FECV turns into FIPV
Internal mutation theory bull Genetic changes from FECV
to FIPV
bull Various types of mutation within OPFs 3 and 7
bull 20 of kittens infected with FECV will produce an FIP mutant
Horizontal (cat-to cat) bull Transmission of FIPV
mutants
bull cats with FIP are shedding the same FIPV in their feces
J Gen Virol 2010 Feb91(Pt 2)415-20 doi 101099vir0016485-0 Epub 2009 Nov 4
Feline infectious peritonitis insights into feline coronavirus
pathobiogenesis and epidemiology based on genetic analysis of the viral
3c gene Chang HW1 de Groot RJ Egberink HF Rottier PJ
helliphellipMost cats with FIP had no detectable intestinal feline coronaviruses (FCoVs) and
had seemingly cleared the primary FECV infection In those with detectable intestinal
FCoV the virus always had an intact 3c and seemed to have been acquired by FECV
superinfection Apparently 3c-inactivated viruses replicate not at all--or only poorly--in the
gut explaining the rare incidence of FIP outbreaks
FIP transmission
FIP transmission
bull Vet Res 2013 Jul 174457 doi 1011861297-9716-44-57
bull An outbreak of feline infectious peritonitis in a Taiwanese shelter epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus
bull Wang YT1 Su BL Hsieh LE Chueh LL
bull Abstract
bull helliphellipSequence analysis revealed that the type II FIPV detected from fecal samples body
effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death Taken together our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment
FCoV field strain in FIP cat
Genomic RNA sequence of feline coronavirus strain FCoV C1Je Charlotte Dye BVMampS PhD CertSAM MRCVS
Stuart G Siddell BSc(Hons) PhD
bull This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV) Viral RNAs isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP) derived 100 nucleotide identity
Feline Coronavirus serotypes I and II were reported in natural infection
bull Feline coronavirus serotypes 1 and 2 seroprevalence and association with disease in Switzerland
bull Clin Diagn Lab Immunol October 200512(10)1209-15 bull Maya Kummrow1 Marina L Meli Michael Haessig Enikoe Goenczi Amy Poland Niels C
Pedersen Regina Hofmann-Lehmann Hans Lutz
bull Comparison of serologic techniques for the detection of antibodies against feline coronaviruses
bull J Vet Diagn Invest January 200820(1)45-50 bull Annamaria Pratelli1
bull Prevalence of Korean cats with natural feline coronavirus infections bull Virol J January 20118(0)455 bull Dong-Jun An1 Hye-Young Jeoung Wooseog Jeong Jee Yong Park Myoung-Heon Lee Bong
Kyun Park bull 1National Veterinary Research and Quarantine Service Anyang Kyunggi-do430-824 Korea
bull Moreshellip
Take home message Knowing ME knowing YOU
My team my world
Thank you
Pyogranulomatous inflammation
FIPV infected monocytes perivascular macrophages overproduce neutrophil survival factors Tumor necrosis factor- alpha (TNF ndashalpha) bull Matrix metalloproyeinase-9 bull GM-CSF bull G-CSF Neutrophil survival Development of granuloma lesions
Interpretation of FCoV antibody test
Viral shedding ~ 2 days (FCoV in epithelial cells)
Signs of FIP
bull As early as 2 wk old to 18 months
bull From pyogranulomatous inflammation to clinical signs may be months
From NC Pederson et al (2008) Feline enteric coronavirus infection
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To rule out FIP in sick cats bull effusive FIP
bull non- effusive FIP ( esp cats with GI signs)
bull To screen the FCoV excretors bull Cats in contact with known FCoV shedder
bull Cats in the household
bull New kitten or new cat bringing into the multi-cat household
bull Before receiving immunosuppressive treatment or stressful procedures
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To screen a breeding queen
bull To monitor FIP treatment q 8-12 wks
bull To screen blood donor cat
bull To screen prior to FeLV vaccination
Blood fluid Interpretation of FCoV antibody test
I false negative in sick FIP cat
II High titer (gt 11600) in normal cat (esp cat from multi-household) is not indicated FIP
III High titer in fluid high PPV
IV Generally not recommended in sick cat
FCoV antibody in CSF
bull Use of anti-coronavirus antibody testing of cerebrospinal fluid for diagnosis of feline infectious peritonitis involving the central nervous system in cats
bull J Am Vet Med Assoc January 2007230(2)199-205
bull Irene C Boettcher1 Tanja Steinberg Kaspar Matiasek Craig E Greene Katrin Hartmann Andrea Fischer
CSF IgG was detected only in strongly seropositive cats suggested that CSF anti-coronavirus IgG was derived from blood Measurement of
anti-coronavirus IgG in CSF was of equivocal clinical use
Test test test
FCoV RT-PCR test ( bloodeffusion fluidfeces)
Blood FCoV RT-PCR FECV Monocyte-associated viremia Not differentiate FIPV from pathotype
FCoV
Fecal FCoV RT-PC Recommend for house-cat management BUT single positive or negative tests are
meaningless as cats may shed intermittently or may be recently infected
Effusion fluid FCoV RT-PCR bull Generally recommended for fluid bull Positive result high PPV bull But 30 of effusions from cats
with FIP may be negative by RT-PCR
Why false negative 1 FIPV is cell-associated and likely confined to cells of perivascular granuloma (leaking out of pure plasma) 2 Inhibition of RT-PCR by interfering substances in fluid Therefore negative result doesnrsquot exclude FIP
Is FIP a contagious disease (cat-to-cat transmission)
Is FIP a contagious disease (cat-to-cat transmission)
Cats with FIP do not excrete pathogenic FIPV
FECV in enterocytes
Is FIP contagious
Cats with FIP do not appear to be very contagious to cats coming in contact with
Every FIPV isolated from a group outbreak of FIP does NOT genetically identical in its 3c gene mutation
However FIPV is found in the feces of most cats with FIP
Mutation when FECV turns into FIPV
Internal mutation theory bull Genetic changes from FECV
to FIPV
bull Various types of mutation within OPFs 3 and 7
bull 20 of kittens infected with FECV will produce an FIP mutant
Horizontal (cat-to cat) bull Transmission of FIPV
mutants
bull cats with FIP are shedding the same FIPV in their feces
J Gen Virol 2010 Feb91(Pt 2)415-20 doi 101099vir0016485-0 Epub 2009 Nov 4
Feline infectious peritonitis insights into feline coronavirus
pathobiogenesis and epidemiology based on genetic analysis of the viral
3c gene Chang HW1 de Groot RJ Egberink HF Rottier PJ
helliphellipMost cats with FIP had no detectable intestinal feline coronaviruses (FCoVs) and
had seemingly cleared the primary FECV infection In those with detectable intestinal
FCoV the virus always had an intact 3c and seemed to have been acquired by FECV
superinfection Apparently 3c-inactivated viruses replicate not at all--or only poorly--in the
gut explaining the rare incidence of FIP outbreaks
FIP transmission
FIP transmission
bull Vet Res 2013 Jul 174457 doi 1011861297-9716-44-57
bull An outbreak of feline infectious peritonitis in a Taiwanese shelter epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus
bull Wang YT1 Su BL Hsieh LE Chueh LL
bull Abstract
bull helliphellipSequence analysis revealed that the type II FIPV detected from fecal samples body
effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death Taken together our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment
FCoV field strain in FIP cat
Genomic RNA sequence of feline coronavirus strain FCoV C1Je Charlotte Dye BVMampS PhD CertSAM MRCVS
Stuart G Siddell BSc(Hons) PhD
bull This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV) Viral RNAs isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP) derived 100 nucleotide identity
Feline Coronavirus serotypes I and II were reported in natural infection
bull Feline coronavirus serotypes 1 and 2 seroprevalence and association with disease in Switzerland
bull Clin Diagn Lab Immunol October 200512(10)1209-15 bull Maya Kummrow1 Marina L Meli Michael Haessig Enikoe Goenczi Amy Poland Niels C
Pedersen Regina Hofmann-Lehmann Hans Lutz
bull Comparison of serologic techniques for the detection of antibodies against feline coronaviruses
bull J Vet Diagn Invest January 200820(1)45-50 bull Annamaria Pratelli1
bull Prevalence of Korean cats with natural feline coronavirus infections bull Virol J January 20118(0)455 bull Dong-Jun An1 Hye-Young Jeoung Wooseog Jeong Jee Yong Park Myoung-Heon Lee Bong
Kyun Park bull 1National Veterinary Research and Quarantine Service Anyang Kyunggi-do430-824 Korea
bull Moreshellip
Take home message Knowing ME knowing YOU
My team my world
Thank you
Interpretation of FCoV antibody test
Viral shedding ~ 2 days (FCoV in epithelial cells)
Signs of FIP
bull As early as 2 wk old to 18 months
bull From pyogranulomatous inflammation to clinical signs may be months
From NC Pederson et al (2008) Feline enteric coronavirus infection
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To rule out FIP in sick cats bull effusive FIP
bull non- effusive FIP ( esp cats with GI signs)
bull To screen the FCoV excretors bull Cats in contact with known FCoV shedder
bull Cats in the household
bull New kitten or new cat bringing into the multi-cat household
bull Before receiving immunosuppressive treatment or stressful procedures
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To screen a breeding queen
bull To monitor FIP treatment q 8-12 wks
bull To screen blood donor cat
bull To screen prior to FeLV vaccination
Blood fluid Interpretation of FCoV antibody test
I false negative in sick FIP cat
II High titer (gt 11600) in normal cat (esp cat from multi-household) is not indicated FIP
III High titer in fluid high PPV
IV Generally not recommended in sick cat
FCoV antibody in CSF
bull Use of anti-coronavirus antibody testing of cerebrospinal fluid for diagnosis of feline infectious peritonitis involving the central nervous system in cats
bull J Am Vet Med Assoc January 2007230(2)199-205
bull Irene C Boettcher1 Tanja Steinberg Kaspar Matiasek Craig E Greene Katrin Hartmann Andrea Fischer
CSF IgG was detected only in strongly seropositive cats suggested that CSF anti-coronavirus IgG was derived from blood Measurement of
anti-coronavirus IgG in CSF was of equivocal clinical use
Test test test
FCoV RT-PCR test ( bloodeffusion fluidfeces)
Blood FCoV RT-PCR FECV Monocyte-associated viremia Not differentiate FIPV from pathotype
FCoV
Fecal FCoV RT-PC Recommend for house-cat management BUT single positive or negative tests are
meaningless as cats may shed intermittently or may be recently infected
Effusion fluid FCoV RT-PCR bull Generally recommended for fluid bull Positive result high PPV bull But 30 of effusions from cats
with FIP may be negative by RT-PCR
Why false negative 1 FIPV is cell-associated and likely confined to cells of perivascular granuloma (leaking out of pure plasma) 2 Inhibition of RT-PCR by interfering substances in fluid Therefore negative result doesnrsquot exclude FIP
Is FIP a contagious disease (cat-to-cat transmission)
Is FIP a contagious disease (cat-to-cat transmission)
Cats with FIP do not excrete pathogenic FIPV
FECV in enterocytes
Is FIP contagious
Cats with FIP do not appear to be very contagious to cats coming in contact with
Every FIPV isolated from a group outbreak of FIP does NOT genetically identical in its 3c gene mutation
However FIPV is found in the feces of most cats with FIP
Mutation when FECV turns into FIPV
Internal mutation theory bull Genetic changes from FECV
to FIPV
bull Various types of mutation within OPFs 3 and 7
bull 20 of kittens infected with FECV will produce an FIP mutant
Horizontal (cat-to cat) bull Transmission of FIPV
mutants
bull cats with FIP are shedding the same FIPV in their feces
J Gen Virol 2010 Feb91(Pt 2)415-20 doi 101099vir0016485-0 Epub 2009 Nov 4
Feline infectious peritonitis insights into feline coronavirus
pathobiogenesis and epidemiology based on genetic analysis of the viral
3c gene Chang HW1 de Groot RJ Egberink HF Rottier PJ
helliphellipMost cats with FIP had no detectable intestinal feline coronaviruses (FCoVs) and
had seemingly cleared the primary FECV infection In those with detectable intestinal
FCoV the virus always had an intact 3c and seemed to have been acquired by FECV
superinfection Apparently 3c-inactivated viruses replicate not at all--or only poorly--in the
gut explaining the rare incidence of FIP outbreaks
FIP transmission
FIP transmission
bull Vet Res 2013 Jul 174457 doi 1011861297-9716-44-57
bull An outbreak of feline infectious peritonitis in a Taiwanese shelter epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus
bull Wang YT1 Su BL Hsieh LE Chueh LL
bull Abstract
bull helliphellipSequence analysis revealed that the type II FIPV detected from fecal samples body
effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death Taken together our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment
FCoV field strain in FIP cat
Genomic RNA sequence of feline coronavirus strain FCoV C1Je Charlotte Dye BVMampS PhD CertSAM MRCVS
Stuart G Siddell BSc(Hons) PhD
bull This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV) Viral RNAs isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP) derived 100 nucleotide identity
Feline Coronavirus serotypes I and II were reported in natural infection
bull Feline coronavirus serotypes 1 and 2 seroprevalence and association with disease in Switzerland
bull Clin Diagn Lab Immunol October 200512(10)1209-15 bull Maya Kummrow1 Marina L Meli Michael Haessig Enikoe Goenczi Amy Poland Niels C
Pedersen Regina Hofmann-Lehmann Hans Lutz
bull Comparison of serologic techniques for the detection of antibodies against feline coronaviruses
bull J Vet Diagn Invest January 200820(1)45-50 bull Annamaria Pratelli1
bull Prevalence of Korean cats with natural feline coronavirus infections bull Virol J January 20118(0)455 bull Dong-Jun An1 Hye-Young Jeoung Wooseog Jeong Jee Yong Park Myoung-Heon Lee Bong
Kyun Park bull 1National Veterinary Research and Quarantine Service Anyang Kyunggi-do430-824 Korea
bull Moreshellip
Take home message Knowing ME knowing YOU
My team my world
Thank you
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To rule out FIP in sick cats bull effusive FIP
bull non- effusive FIP ( esp cats with GI signs)
bull To screen the FCoV excretors bull Cats in contact with known FCoV shedder
bull Cats in the household
bull New kitten or new cat bringing into the multi-cat household
bull Before receiving immunosuppressive treatment or stressful procedures
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To screen a breeding queen
bull To monitor FIP treatment q 8-12 wks
bull To screen blood donor cat
bull To screen prior to FeLV vaccination
Blood fluid Interpretation of FCoV antibody test
I false negative in sick FIP cat
II High titer (gt 11600) in normal cat (esp cat from multi-household) is not indicated FIP
III High titer in fluid high PPV
IV Generally not recommended in sick cat
FCoV antibody in CSF
bull Use of anti-coronavirus antibody testing of cerebrospinal fluid for diagnosis of feline infectious peritonitis involving the central nervous system in cats
bull J Am Vet Med Assoc January 2007230(2)199-205
bull Irene C Boettcher1 Tanja Steinberg Kaspar Matiasek Craig E Greene Katrin Hartmann Andrea Fischer
CSF IgG was detected only in strongly seropositive cats suggested that CSF anti-coronavirus IgG was derived from blood Measurement of
anti-coronavirus IgG in CSF was of equivocal clinical use
Test test test
FCoV RT-PCR test ( bloodeffusion fluidfeces)
Blood FCoV RT-PCR FECV Monocyte-associated viremia Not differentiate FIPV from pathotype
FCoV
Fecal FCoV RT-PC Recommend for house-cat management BUT single positive or negative tests are
meaningless as cats may shed intermittently or may be recently infected
Effusion fluid FCoV RT-PCR bull Generally recommended for fluid bull Positive result high PPV bull But 30 of effusions from cats
with FIP may be negative by RT-PCR
Why false negative 1 FIPV is cell-associated and likely confined to cells of perivascular granuloma (leaking out of pure plasma) 2 Inhibition of RT-PCR by interfering substances in fluid Therefore negative result doesnrsquot exclude FIP
Is FIP a contagious disease (cat-to-cat transmission)
Is FIP a contagious disease (cat-to-cat transmission)
Cats with FIP do not excrete pathogenic FIPV
FECV in enterocytes
Is FIP contagious
Cats with FIP do not appear to be very contagious to cats coming in contact with
Every FIPV isolated from a group outbreak of FIP does NOT genetically identical in its 3c gene mutation
However FIPV is found in the feces of most cats with FIP
Mutation when FECV turns into FIPV
Internal mutation theory bull Genetic changes from FECV
to FIPV
bull Various types of mutation within OPFs 3 and 7
bull 20 of kittens infected with FECV will produce an FIP mutant
Horizontal (cat-to cat) bull Transmission of FIPV
mutants
bull cats with FIP are shedding the same FIPV in their feces
J Gen Virol 2010 Feb91(Pt 2)415-20 doi 101099vir0016485-0 Epub 2009 Nov 4
Feline infectious peritonitis insights into feline coronavirus
pathobiogenesis and epidemiology based on genetic analysis of the viral
3c gene Chang HW1 de Groot RJ Egberink HF Rottier PJ
helliphellipMost cats with FIP had no detectable intestinal feline coronaviruses (FCoVs) and
had seemingly cleared the primary FECV infection In those with detectable intestinal
FCoV the virus always had an intact 3c and seemed to have been acquired by FECV
superinfection Apparently 3c-inactivated viruses replicate not at all--or only poorly--in the
gut explaining the rare incidence of FIP outbreaks
FIP transmission
FIP transmission
bull Vet Res 2013 Jul 174457 doi 1011861297-9716-44-57
bull An outbreak of feline infectious peritonitis in a Taiwanese shelter epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus
bull Wang YT1 Su BL Hsieh LE Chueh LL
bull Abstract
bull helliphellipSequence analysis revealed that the type II FIPV detected from fecal samples body
effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death Taken together our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment
FCoV field strain in FIP cat
Genomic RNA sequence of feline coronavirus strain FCoV C1Je Charlotte Dye BVMampS PhD CertSAM MRCVS
Stuart G Siddell BSc(Hons) PhD
bull This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV) Viral RNAs isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP) derived 100 nucleotide identity
Feline Coronavirus serotypes I and II were reported in natural infection
bull Feline coronavirus serotypes 1 and 2 seroprevalence and association with disease in Switzerland
bull Clin Diagn Lab Immunol October 200512(10)1209-15 bull Maya Kummrow1 Marina L Meli Michael Haessig Enikoe Goenczi Amy Poland Niels C
Pedersen Regina Hofmann-Lehmann Hans Lutz
bull Comparison of serologic techniques for the detection of antibodies against feline coronaviruses
bull J Vet Diagn Invest January 200820(1)45-50 bull Annamaria Pratelli1
bull Prevalence of Korean cats with natural feline coronavirus infections bull Virol J January 20118(0)455 bull Dong-Jun An1 Hye-Young Jeoung Wooseog Jeong Jee Yong Park Myoung-Heon Lee Bong
Kyun Park bull 1National Veterinary Research and Quarantine Service Anyang Kyunggi-do430-824 Korea
bull Moreshellip
Take home message Knowing ME knowing YOU
My team my world
Thank you
When is ldquoin-houserdquo FCoV antibody test required Which test
bull To screen a breeding queen
bull To monitor FIP treatment q 8-12 wks
bull To screen blood donor cat
bull To screen prior to FeLV vaccination
Blood fluid Interpretation of FCoV antibody test
I false negative in sick FIP cat
II High titer (gt 11600) in normal cat (esp cat from multi-household) is not indicated FIP
III High titer in fluid high PPV
IV Generally not recommended in sick cat
FCoV antibody in CSF
bull Use of anti-coronavirus antibody testing of cerebrospinal fluid for diagnosis of feline infectious peritonitis involving the central nervous system in cats
bull J Am Vet Med Assoc January 2007230(2)199-205
bull Irene C Boettcher1 Tanja Steinberg Kaspar Matiasek Craig E Greene Katrin Hartmann Andrea Fischer
CSF IgG was detected only in strongly seropositive cats suggested that CSF anti-coronavirus IgG was derived from blood Measurement of
anti-coronavirus IgG in CSF was of equivocal clinical use
Test test test
FCoV RT-PCR test ( bloodeffusion fluidfeces)
Blood FCoV RT-PCR FECV Monocyte-associated viremia Not differentiate FIPV from pathotype
FCoV
Fecal FCoV RT-PC Recommend for house-cat management BUT single positive or negative tests are
meaningless as cats may shed intermittently or may be recently infected
Effusion fluid FCoV RT-PCR bull Generally recommended for fluid bull Positive result high PPV bull But 30 of effusions from cats
with FIP may be negative by RT-PCR
Why false negative 1 FIPV is cell-associated and likely confined to cells of perivascular granuloma (leaking out of pure plasma) 2 Inhibition of RT-PCR by interfering substances in fluid Therefore negative result doesnrsquot exclude FIP
Is FIP a contagious disease (cat-to-cat transmission)
Is FIP a contagious disease (cat-to-cat transmission)
Cats with FIP do not excrete pathogenic FIPV
FECV in enterocytes
Is FIP contagious
Cats with FIP do not appear to be very contagious to cats coming in contact with
Every FIPV isolated from a group outbreak of FIP does NOT genetically identical in its 3c gene mutation
However FIPV is found in the feces of most cats with FIP
Mutation when FECV turns into FIPV
Internal mutation theory bull Genetic changes from FECV
to FIPV
bull Various types of mutation within OPFs 3 and 7
bull 20 of kittens infected with FECV will produce an FIP mutant
Horizontal (cat-to cat) bull Transmission of FIPV
mutants
bull cats with FIP are shedding the same FIPV in their feces
J Gen Virol 2010 Feb91(Pt 2)415-20 doi 101099vir0016485-0 Epub 2009 Nov 4
Feline infectious peritonitis insights into feline coronavirus
pathobiogenesis and epidemiology based on genetic analysis of the viral
3c gene Chang HW1 de Groot RJ Egberink HF Rottier PJ
helliphellipMost cats with FIP had no detectable intestinal feline coronaviruses (FCoVs) and
had seemingly cleared the primary FECV infection In those with detectable intestinal
FCoV the virus always had an intact 3c and seemed to have been acquired by FECV
superinfection Apparently 3c-inactivated viruses replicate not at all--or only poorly--in the
gut explaining the rare incidence of FIP outbreaks
FIP transmission
FIP transmission
bull Vet Res 2013 Jul 174457 doi 1011861297-9716-44-57
bull An outbreak of feline infectious peritonitis in a Taiwanese shelter epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus
bull Wang YT1 Su BL Hsieh LE Chueh LL
bull Abstract
bull helliphellipSequence analysis revealed that the type II FIPV detected from fecal samples body
effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death Taken together our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment
FCoV field strain in FIP cat
Genomic RNA sequence of feline coronavirus strain FCoV C1Je Charlotte Dye BVMampS PhD CertSAM MRCVS
Stuart G Siddell BSc(Hons) PhD
bull This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV) Viral RNAs isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP) derived 100 nucleotide identity
Feline Coronavirus serotypes I and II were reported in natural infection
bull Feline coronavirus serotypes 1 and 2 seroprevalence and association with disease in Switzerland
bull Clin Diagn Lab Immunol October 200512(10)1209-15 bull Maya Kummrow1 Marina L Meli Michael Haessig Enikoe Goenczi Amy Poland Niels C
Pedersen Regina Hofmann-Lehmann Hans Lutz
bull Comparison of serologic techniques for the detection of antibodies against feline coronaviruses
bull J Vet Diagn Invest January 200820(1)45-50 bull Annamaria Pratelli1
bull Prevalence of Korean cats with natural feline coronavirus infections bull Virol J January 20118(0)455 bull Dong-Jun An1 Hye-Young Jeoung Wooseog Jeong Jee Yong Park Myoung-Heon Lee Bong
Kyun Park bull 1National Veterinary Research and Quarantine Service Anyang Kyunggi-do430-824 Korea
bull Moreshellip
Take home message Knowing ME knowing YOU
My team my world
Thank you
Blood fluid Interpretation of FCoV antibody test
I false negative in sick FIP cat
II High titer (gt 11600) in normal cat (esp cat from multi-household) is not indicated FIP
III High titer in fluid high PPV
IV Generally not recommended in sick cat
FCoV antibody in CSF
bull Use of anti-coronavirus antibody testing of cerebrospinal fluid for diagnosis of feline infectious peritonitis involving the central nervous system in cats
bull J Am Vet Med Assoc January 2007230(2)199-205
bull Irene C Boettcher1 Tanja Steinberg Kaspar Matiasek Craig E Greene Katrin Hartmann Andrea Fischer
CSF IgG was detected only in strongly seropositive cats suggested that CSF anti-coronavirus IgG was derived from blood Measurement of
anti-coronavirus IgG in CSF was of equivocal clinical use
Test test test
FCoV RT-PCR test ( bloodeffusion fluidfeces)
Blood FCoV RT-PCR FECV Monocyte-associated viremia Not differentiate FIPV from pathotype
FCoV
Fecal FCoV RT-PC Recommend for house-cat management BUT single positive or negative tests are
meaningless as cats may shed intermittently or may be recently infected
Effusion fluid FCoV RT-PCR bull Generally recommended for fluid bull Positive result high PPV bull But 30 of effusions from cats
with FIP may be negative by RT-PCR
Why false negative 1 FIPV is cell-associated and likely confined to cells of perivascular granuloma (leaking out of pure plasma) 2 Inhibition of RT-PCR by interfering substances in fluid Therefore negative result doesnrsquot exclude FIP
Is FIP a contagious disease (cat-to-cat transmission)
Is FIP a contagious disease (cat-to-cat transmission)
Cats with FIP do not excrete pathogenic FIPV
FECV in enterocytes
Is FIP contagious
Cats with FIP do not appear to be very contagious to cats coming in contact with
Every FIPV isolated from a group outbreak of FIP does NOT genetically identical in its 3c gene mutation
However FIPV is found in the feces of most cats with FIP
Mutation when FECV turns into FIPV
Internal mutation theory bull Genetic changes from FECV
to FIPV
bull Various types of mutation within OPFs 3 and 7
bull 20 of kittens infected with FECV will produce an FIP mutant
Horizontal (cat-to cat) bull Transmission of FIPV
mutants
bull cats with FIP are shedding the same FIPV in their feces
J Gen Virol 2010 Feb91(Pt 2)415-20 doi 101099vir0016485-0 Epub 2009 Nov 4
Feline infectious peritonitis insights into feline coronavirus
pathobiogenesis and epidemiology based on genetic analysis of the viral
3c gene Chang HW1 de Groot RJ Egberink HF Rottier PJ
helliphellipMost cats with FIP had no detectable intestinal feline coronaviruses (FCoVs) and
had seemingly cleared the primary FECV infection In those with detectable intestinal
FCoV the virus always had an intact 3c and seemed to have been acquired by FECV
superinfection Apparently 3c-inactivated viruses replicate not at all--or only poorly--in the
gut explaining the rare incidence of FIP outbreaks
FIP transmission
FIP transmission
bull Vet Res 2013 Jul 174457 doi 1011861297-9716-44-57
bull An outbreak of feline infectious peritonitis in a Taiwanese shelter epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus
bull Wang YT1 Su BL Hsieh LE Chueh LL
bull Abstract
bull helliphellipSequence analysis revealed that the type II FIPV detected from fecal samples body
effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death Taken together our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment
FCoV field strain in FIP cat
Genomic RNA sequence of feline coronavirus strain FCoV C1Je Charlotte Dye BVMampS PhD CertSAM MRCVS
Stuart G Siddell BSc(Hons) PhD
bull This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV) Viral RNAs isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP) derived 100 nucleotide identity
Feline Coronavirus serotypes I and II were reported in natural infection
bull Feline coronavirus serotypes 1 and 2 seroprevalence and association with disease in Switzerland
bull Clin Diagn Lab Immunol October 200512(10)1209-15 bull Maya Kummrow1 Marina L Meli Michael Haessig Enikoe Goenczi Amy Poland Niels C
Pedersen Regina Hofmann-Lehmann Hans Lutz
bull Comparison of serologic techniques for the detection of antibodies against feline coronaviruses
bull J Vet Diagn Invest January 200820(1)45-50 bull Annamaria Pratelli1
bull Prevalence of Korean cats with natural feline coronavirus infections bull Virol J January 20118(0)455 bull Dong-Jun An1 Hye-Young Jeoung Wooseog Jeong Jee Yong Park Myoung-Heon Lee Bong
Kyun Park bull 1National Veterinary Research and Quarantine Service Anyang Kyunggi-do430-824 Korea
bull Moreshellip
Take home message Knowing ME knowing YOU
My team my world
Thank you
FCoV antibody in CSF
bull Use of anti-coronavirus antibody testing of cerebrospinal fluid for diagnosis of feline infectious peritonitis involving the central nervous system in cats
bull J Am Vet Med Assoc January 2007230(2)199-205
bull Irene C Boettcher1 Tanja Steinberg Kaspar Matiasek Craig E Greene Katrin Hartmann Andrea Fischer
CSF IgG was detected only in strongly seropositive cats suggested that CSF anti-coronavirus IgG was derived from blood Measurement of
anti-coronavirus IgG in CSF was of equivocal clinical use
Test test test
FCoV RT-PCR test ( bloodeffusion fluidfeces)
Blood FCoV RT-PCR FECV Monocyte-associated viremia Not differentiate FIPV from pathotype
FCoV
Fecal FCoV RT-PC Recommend for house-cat management BUT single positive or negative tests are
meaningless as cats may shed intermittently or may be recently infected
Effusion fluid FCoV RT-PCR bull Generally recommended for fluid bull Positive result high PPV bull But 30 of effusions from cats
with FIP may be negative by RT-PCR
Why false negative 1 FIPV is cell-associated and likely confined to cells of perivascular granuloma (leaking out of pure plasma) 2 Inhibition of RT-PCR by interfering substances in fluid Therefore negative result doesnrsquot exclude FIP
Is FIP a contagious disease (cat-to-cat transmission)
Is FIP a contagious disease (cat-to-cat transmission)
Cats with FIP do not excrete pathogenic FIPV
FECV in enterocytes
Is FIP contagious
Cats with FIP do not appear to be very contagious to cats coming in contact with
Every FIPV isolated from a group outbreak of FIP does NOT genetically identical in its 3c gene mutation
However FIPV is found in the feces of most cats with FIP
Mutation when FECV turns into FIPV
Internal mutation theory bull Genetic changes from FECV
to FIPV
bull Various types of mutation within OPFs 3 and 7
bull 20 of kittens infected with FECV will produce an FIP mutant
Horizontal (cat-to cat) bull Transmission of FIPV
mutants
bull cats with FIP are shedding the same FIPV in their feces
J Gen Virol 2010 Feb91(Pt 2)415-20 doi 101099vir0016485-0 Epub 2009 Nov 4
Feline infectious peritonitis insights into feline coronavirus
pathobiogenesis and epidemiology based on genetic analysis of the viral
3c gene Chang HW1 de Groot RJ Egberink HF Rottier PJ
helliphellipMost cats with FIP had no detectable intestinal feline coronaviruses (FCoVs) and
had seemingly cleared the primary FECV infection In those with detectable intestinal
FCoV the virus always had an intact 3c and seemed to have been acquired by FECV
superinfection Apparently 3c-inactivated viruses replicate not at all--or only poorly--in the
gut explaining the rare incidence of FIP outbreaks
FIP transmission
FIP transmission
bull Vet Res 2013 Jul 174457 doi 1011861297-9716-44-57
bull An outbreak of feline infectious peritonitis in a Taiwanese shelter epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus
bull Wang YT1 Su BL Hsieh LE Chueh LL
bull Abstract
bull helliphellipSequence analysis revealed that the type II FIPV detected from fecal samples body
effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death Taken together our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment
FCoV field strain in FIP cat
Genomic RNA sequence of feline coronavirus strain FCoV C1Je Charlotte Dye BVMampS PhD CertSAM MRCVS
Stuart G Siddell BSc(Hons) PhD
bull This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV) Viral RNAs isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP) derived 100 nucleotide identity
Feline Coronavirus serotypes I and II were reported in natural infection
bull Feline coronavirus serotypes 1 and 2 seroprevalence and association with disease in Switzerland
bull Clin Diagn Lab Immunol October 200512(10)1209-15 bull Maya Kummrow1 Marina L Meli Michael Haessig Enikoe Goenczi Amy Poland Niels C
Pedersen Regina Hofmann-Lehmann Hans Lutz
bull Comparison of serologic techniques for the detection of antibodies against feline coronaviruses
bull J Vet Diagn Invest January 200820(1)45-50 bull Annamaria Pratelli1
bull Prevalence of Korean cats with natural feline coronavirus infections bull Virol J January 20118(0)455 bull Dong-Jun An1 Hye-Young Jeoung Wooseog Jeong Jee Yong Park Myoung-Heon Lee Bong
Kyun Park bull 1National Veterinary Research and Quarantine Service Anyang Kyunggi-do430-824 Korea
bull Moreshellip
Take home message Knowing ME knowing YOU
My team my world
Thank you
Test test test
FCoV RT-PCR test ( bloodeffusion fluidfeces)
Blood FCoV RT-PCR FECV Monocyte-associated viremia Not differentiate FIPV from pathotype
FCoV
Fecal FCoV RT-PC Recommend for house-cat management BUT single positive or negative tests are
meaningless as cats may shed intermittently or may be recently infected
Effusion fluid FCoV RT-PCR bull Generally recommended for fluid bull Positive result high PPV bull But 30 of effusions from cats
with FIP may be negative by RT-PCR
Why false negative 1 FIPV is cell-associated and likely confined to cells of perivascular granuloma (leaking out of pure plasma) 2 Inhibition of RT-PCR by interfering substances in fluid Therefore negative result doesnrsquot exclude FIP
Is FIP a contagious disease (cat-to-cat transmission)
Is FIP a contagious disease (cat-to-cat transmission)
Cats with FIP do not excrete pathogenic FIPV
FECV in enterocytes
Is FIP contagious
Cats with FIP do not appear to be very contagious to cats coming in contact with
Every FIPV isolated from a group outbreak of FIP does NOT genetically identical in its 3c gene mutation
However FIPV is found in the feces of most cats with FIP
Mutation when FECV turns into FIPV
Internal mutation theory bull Genetic changes from FECV
to FIPV
bull Various types of mutation within OPFs 3 and 7
bull 20 of kittens infected with FECV will produce an FIP mutant
Horizontal (cat-to cat) bull Transmission of FIPV
mutants
bull cats with FIP are shedding the same FIPV in their feces
J Gen Virol 2010 Feb91(Pt 2)415-20 doi 101099vir0016485-0 Epub 2009 Nov 4
Feline infectious peritonitis insights into feline coronavirus
pathobiogenesis and epidemiology based on genetic analysis of the viral
3c gene Chang HW1 de Groot RJ Egberink HF Rottier PJ
helliphellipMost cats with FIP had no detectable intestinal feline coronaviruses (FCoVs) and
had seemingly cleared the primary FECV infection In those with detectable intestinal
FCoV the virus always had an intact 3c and seemed to have been acquired by FECV
superinfection Apparently 3c-inactivated viruses replicate not at all--or only poorly--in the
gut explaining the rare incidence of FIP outbreaks
FIP transmission
FIP transmission
bull Vet Res 2013 Jul 174457 doi 1011861297-9716-44-57
bull An outbreak of feline infectious peritonitis in a Taiwanese shelter epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus
bull Wang YT1 Su BL Hsieh LE Chueh LL
bull Abstract
bull helliphellipSequence analysis revealed that the type II FIPV detected from fecal samples body
effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death Taken together our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment
FCoV field strain in FIP cat
Genomic RNA sequence of feline coronavirus strain FCoV C1Je Charlotte Dye BVMampS PhD CertSAM MRCVS
Stuart G Siddell BSc(Hons) PhD
bull This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV) Viral RNAs isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP) derived 100 nucleotide identity
Feline Coronavirus serotypes I and II were reported in natural infection
bull Feline coronavirus serotypes 1 and 2 seroprevalence and association with disease in Switzerland
bull Clin Diagn Lab Immunol October 200512(10)1209-15 bull Maya Kummrow1 Marina L Meli Michael Haessig Enikoe Goenczi Amy Poland Niels C
Pedersen Regina Hofmann-Lehmann Hans Lutz
bull Comparison of serologic techniques for the detection of antibodies against feline coronaviruses
bull J Vet Diagn Invest January 200820(1)45-50 bull Annamaria Pratelli1
bull Prevalence of Korean cats with natural feline coronavirus infections bull Virol J January 20118(0)455 bull Dong-Jun An1 Hye-Young Jeoung Wooseog Jeong Jee Yong Park Myoung-Heon Lee Bong
Kyun Park bull 1National Veterinary Research and Quarantine Service Anyang Kyunggi-do430-824 Korea
bull Moreshellip
Take home message Knowing ME knowing YOU
My team my world
Thank you
FCoV RT-PCR test ( bloodeffusion fluidfeces)
Blood FCoV RT-PCR FECV Monocyte-associated viremia Not differentiate FIPV from pathotype
FCoV
Fecal FCoV RT-PC Recommend for house-cat management BUT single positive or negative tests are
meaningless as cats may shed intermittently or may be recently infected
Effusion fluid FCoV RT-PCR bull Generally recommended for fluid bull Positive result high PPV bull But 30 of effusions from cats
with FIP may be negative by RT-PCR
Why false negative 1 FIPV is cell-associated and likely confined to cells of perivascular granuloma (leaking out of pure plasma) 2 Inhibition of RT-PCR by interfering substances in fluid Therefore negative result doesnrsquot exclude FIP
Is FIP a contagious disease (cat-to-cat transmission)
Is FIP a contagious disease (cat-to-cat transmission)
Cats with FIP do not excrete pathogenic FIPV
FECV in enterocytes
Is FIP contagious
Cats with FIP do not appear to be very contagious to cats coming in contact with
Every FIPV isolated from a group outbreak of FIP does NOT genetically identical in its 3c gene mutation
However FIPV is found in the feces of most cats with FIP
Mutation when FECV turns into FIPV
Internal mutation theory bull Genetic changes from FECV
to FIPV
bull Various types of mutation within OPFs 3 and 7
bull 20 of kittens infected with FECV will produce an FIP mutant
Horizontal (cat-to cat) bull Transmission of FIPV
mutants
bull cats with FIP are shedding the same FIPV in their feces
J Gen Virol 2010 Feb91(Pt 2)415-20 doi 101099vir0016485-0 Epub 2009 Nov 4
Feline infectious peritonitis insights into feline coronavirus
pathobiogenesis and epidemiology based on genetic analysis of the viral
3c gene Chang HW1 de Groot RJ Egberink HF Rottier PJ
helliphellipMost cats with FIP had no detectable intestinal feline coronaviruses (FCoVs) and
had seemingly cleared the primary FECV infection In those with detectable intestinal
FCoV the virus always had an intact 3c and seemed to have been acquired by FECV
superinfection Apparently 3c-inactivated viruses replicate not at all--or only poorly--in the
gut explaining the rare incidence of FIP outbreaks
FIP transmission
FIP transmission
bull Vet Res 2013 Jul 174457 doi 1011861297-9716-44-57
bull An outbreak of feline infectious peritonitis in a Taiwanese shelter epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus
bull Wang YT1 Su BL Hsieh LE Chueh LL
bull Abstract
bull helliphellipSequence analysis revealed that the type II FIPV detected from fecal samples body
effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death Taken together our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment
FCoV field strain in FIP cat
Genomic RNA sequence of feline coronavirus strain FCoV C1Je Charlotte Dye BVMampS PhD CertSAM MRCVS
Stuart G Siddell BSc(Hons) PhD
bull This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV) Viral RNAs isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP) derived 100 nucleotide identity
Feline Coronavirus serotypes I and II were reported in natural infection
bull Feline coronavirus serotypes 1 and 2 seroprevalence and association with disease in Switzerland
bull Clin Diagn Lab Immunol October 200512(10)1209-15 bull Maya Kummrow1 Marina L Meli Michael Haessig Enikoe Goenczi Amy Poland Niels C
Pedersen Regina Hofmann-Lehmann Hans Lutz
bull Comparison of serologic techniques for the detection of antibodies against feline coronaviruses
bull J Vet Diagn Invest January 200820(1)45-50 bull Annamaria Pratelli1
bull Prevalence of Korean cats with natural feline coronavirus infections bull Virol J January 20118(0)455 bull Dong-Jun An1 Hye-Young Jeoung Wooseog Jeong Jee Yong Park Myoung-Heon Lee Bong
Kyun Park bull 1National Veterinary Research and Quarantine Service Anyang Kyunggi-do430-824 Korea
bull Moreshellip
Take home message Knowing ME knowing YOU
My team my world
Thank you
Is FIP a contagious disease (cat-to-cat transmission)
Is FIP a contagious disease (cat-to-cat transmission)
Cats with FIP do not excrete pathogenic FIPV
FECV in enterocytes
Is FIP contagious
Cats with FIP do not appear to be very contagious to cats coming in contact with
Every FIPV isolated from a group outbreak of FIP does NOT genetically identical in its 3c gene mutation
However FIPV is found in the feces of most cats with FIP
Mutation when FECV turns into FIPV
Internal mutation theory bull Genetic changes from FECV
to FIPV
bull Various types of mutation within OPFs 3 and 7
bull 20 of kittens infected with FECV will produce an FIP mutant
Horizontal (cat-to cat) bull Transmission of FIPV
mutants
bull cats with FIP are shedding the same FIPV in their feces
J Gen Virol 2010 Feb91(Pt 2)415-20 doi 101099vir0016485-0 Epub 2009 Nov 4
Feline infectious peritonitis insights into feline coronavirus
pathobiogenesis and epidemiology based on genetic analysis of the viral
3c gene Chang HW1 de Groot RJ Egberink HF Rottier PJ
helliphellipMost cats with FIP had no detectable intestinal feline coronaviruses (FCoVs) and
had seemingly cleared the primary FECV infection In those with detectable intestinal
FCoV the virus always had an intact 3c and seemed to have been acquired by FECV
superinfection Apparently 3c-inactivated viruses replicate not at all--or only poorly--in the
gut explaining the rare incidence of FIP outbreaks
FIP transmission
FIP transmission
bull Vet Res 2013 Jul 174457 doi 1011861297-9716-44-57
bull An outbreak of feline infectious peritonitis in a Taiwanese shelter epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus
bull Wang YT1 Su BL Hsieh LE Chueh LL
bull Abstract
bull helliphellipSequence analysis revealed that the type II FIPV detected from fecal samples body
effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death Taken together our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment
FCoV field strain in FIP cat
Genomic RNA sequence of feline coronavirus strain FCoV C1Je Charlotte Dye BVMampS PhD CertSAM MRCVS
Stuart G Siddell BSc(Hons) PhD
bull This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV) Viral RNAs isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP) derived 100 nucleotide identity
Feline Coronavirus serotypes I and II were reported in natural infection
bull Feline coronavirus serotypes 1 and 2 seroprevalence and association with disease in Switzerland
bull Clin Diagn Lab Immunol October 200512(10)1209-15 bull Maya Kummrow1 Marina L Meli Michael Haessig Enikoe Goenczi Amy Poland Niels C
Pedersen Regina Hofmann-Lehmann Hans Lutz
bull Comparison of serologic techniques for the detection of antibodies against feline coronaviruses
bull J Vet Diagn Invest January 200820(1)45-50 bull Annamaria Pratelli1
bull Prevalence of Korean cats with natural feline coronavirus infections bull Virol J January 20118(0)455 bull Dong-Jun An1 Hye-Young Jeoung Wooseog Jeong Jee Yong Park Myoung-Heon Lee Bong
Kyun Park bull 1National Veterinary Research and Quarantine Service Anyang Kyunggi-do430-824 Korea
bull Moreshellip
Take home message Knowing ME knowing YOU
My team my world
Thank you
Is FIP a contagious disease (cat-to-cat transmission)
Cats with FIP do not excrete pathogenic FIPV
FECV in enterocytes
Is FIP contagious
Cats with FIP do not appear to be very contagious to cats coming in contact with
Every FIPV isolated from a group outbreak of FIP does NOT genetically identical in its 3c gene mutation
However FIPV is found in the feces of most cats with FIP
Mutation when FECV turns into FIPV
Internal mutation theory bull Genetic changes from FECV
to FIPV
bull Various types of mutation within OPFs 3 and 7
bull 20 of kittens infected with FECV will produce an FIP mutant
Horizontal (cat-to cat) bull Transmission of FIPV
mutants
bull cats with FIP are shedding the same FIPV in their feces
J Gen Virol 2010 Feb91(Pt 2)415-20 doi 101099vir0016485-0 Epub 2009 Nov 4
Feline infectious peritonitis insights into feline coronavirus
pathobiogenesis and epidemiology based on genetic analysis of the viral
3c gene Chang HW1 de Groot RJ Egberink HF Rottier PJ
helliphellipMost cats with FIP had no detectable intestinal feline coronaviruses (FCoVs) and
had seemingly cleared the primary FECV infection In those with detectable intestinal
FCoV the virus always had an intact 3c and seemed to have been acquired by FECV
superinfection Apparently 3c-inactivated viruses replicate not at all--or only poorly--in the
gut explaining the rare incidence of FIP outbreaks
FIP transmission
FIP transmission
bull Vet Res 2013 Jul 174457 doi 1011861297-9716-44-57
bull An outbreak of feline infectious peritonitis in a Taiwanese shelter epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus
bull Wang YT1 Su BL Hsieh LE Chueh LL
bull Abstract
bull helliphellipSequence analysis revealed that the type II FIPV detected from fecal samples body
effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death Taken together our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment
FCoV field strain in FIP cat
Genomic RNA sequence of feline coronavirus strain FCoV C1Je Charlotte Dye BVMampS PhD CertSAM MRCVS
Stuart G Siddell BSc(Hons) PhD
bull This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV) Viral RNAs isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP) derived 100 nucleotide identity
Feline Coronavirus serotypes I and II were reported in natural infection
bull Feline coronavirus serotypes 1 and 2 seroprevalence and association with disease in Switzerland
bull Clin Diagn Lab Immunol October 200512(10)1209-15 bull Maya Kummrow1 Marina L Meli Michael Haessig Enikoe Goenczi Amy Poland Niels C
Pedersen Regina Hofmann-Lehmann Hans Lutz
bull Comparison of serologic techniques for the detection of antibodies against feline coronaviruses
bull J Vet Diagn Invest January 200820(1)45-50 bull Annamaria Pratelli1
bull Prevalence of Korean cats with natural feline coronavirus infections bull Virol J January 20118(0)455 bull Dong-Jun An1 Hye-Young Jeoung Wooseog Jeong Jee Yong Park Myoung-Heon Lee Bong
Kyun Park bull 1National Veterinary Research and Quarantine Service Anyang Kyunggi-do430-824 Korea
bull Moreshellip
Take home message Knowing ME knowing YOU
My team my world
Thank you
Is FIP contagious
Cats with FIP do not appear to be very contagious to cats coming in contact with
Every FIPV isolated from a group outbreak of FIP does NOT genetically identical in its 3c gene mutation
However FIPV is found in the feces of most cats with FIP
Mutation when FECV turns into FIPV
Internal mutation theory bull Genetic changes from FECV
to FIPV
bull Various types of mutation within OPFs 3 and 7
bull 20 of kittens infected with FECV will produce an FIP mutant
Horizontal (cat-to cat) bull Transmission of FIPV
mutants
bull cats with FIP are shedding the same FIPV in their feces
J Gen Virol 2010 Feb91(Pt 2)415-20 doi 101099vir0016485-0 Epub 2009 Nov 4
Feline infectious peritonitis insights into feline coronavirus
pathobiogenesis and epidemiology based on genetic analysis of the viral
3c gene Chang HW1 de Groot RJ Egberink HF Rottier PJ
helliphellipMost cats with FIP had no detectable intestinal feline coronaviruses (FCoVs) and
had seemingly cleared the primary FECV infection In those with detectable intestinal
FCoV the virus always had an intact 3c and seemed to have been acquired by FECV
superinfection Apparently 3c-inactivated viruses replicate not at all--or only poorly--in the
gut explaining the rare incidence of FIP outbreaks
FIP transmission
FIP transmission
bull Vet Res 2013 Jul 174457 doi 1011861297-9716-44-57
bull An outbreak of feline infectious peritonitis in a Taiwanese shelter epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus
bull Wang YT1 Su BL Hsieh LE Chueh LL
bull Abstract
bull helliphellipSequence analysis revealed that the type II FIPV detected from fecal samples body
effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death Taken together our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment
FCoV field strain in FIP cat
Genomic RNA sequence of feline coronavirus strain FCoV C1Je Charlotte Dye BVMampS PhD CertSAM MRCVS
Stuart G Siddell BSc(Hons) PhD
bull This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV) Viral RNAs isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP) derived 100 nucleotide identity
Feline Coronavirus serotypes I and II were reported in natural infection
bull Feline coronavirus serotypes 1 and 2 seroprevalence and association with disease in Switzerland
bull Clin Diagn Lab Immunol October 200512(10)1209-15 bull Maya Kummrow1 Marina L Meli Michael Haessig Enikoe Goenczi Amy Poland Niels C
Pedersen Regina Hofmann-Lehmann Hans Lutz
bull Comparison of serologic techniques for the detection of antibodies against feline coronaviruses
bull J Vet Diagn Invest January 200820(1)45-50 bull Annamaria Pratelli1
bull Prevalence of Korean cats with natural feline coronavirus infections bull Virol J January 20118(0)455 bull Dong-Jun An1 Hye-Young Jeoung Wooseog Jeong Jee Yong Park Myoung-Heon Lee Bong
Kyun Park bull 1National Veterinary Research and Quarantine Service Anyang Kyunggi-do430-824 Korea
bull Moreshellip
Take home message Knowing ME knowing YOU
My team my world
Thank you
Mutation when FECV turns into FIPV
Internal mutation theory bull Genetic changes from FECV
to FIPV
bull Various types of mutation within OPFs 3 and 7
bull 20 of kittens infected with FECV will produce an FIP mutant
Horizontal (cat-to cat) bull Transmission of FIPV
mutants
bull cats with FIP are shedding the same FIPV in their feces
J Gen Virol 2010 Feb91(Pt 2)415-20 doi 101099vir0016485-0 Epub 2009 Nov 4
Feline infectious peritonitis insights into feline coronavirus
pathobiogenesis and epidemiology based on genetic analysis of the viral
3c gene Chang HW1 de Groot RJ Egberink HF Rottier PJ
helliphellipMost cats with FIP had no detectable intestinal feline coronaviruses (FCoVs) and
had seemingly cleared the primary FECV infection In those with detectable intestinal
FCoV the virus always had an intact 3c and seemed to have been acquired by FECV
superinfection Apparently 3c-inactivated viruses replicate not at all--or only poorly--in the
gut explaining the rare incidence of FIP outbreaks
FIP transmission
FIP transmission
bull Vet Res 2013 Jul 174457 doi 1011861297-9716-44-57
bull An outbreak of feline infectious peritonitis in a Taiwanese shelter epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus
bull Wang YT1 Su BL Hsieh LE Chueh LL
bull Abstract
bull helliphellipSequence analysis revealed that the type II FIPV detected from fecal samples body
effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death Taken together our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment
FCoV field strain in FIP cat
Genomic RNA sequence of feline coronavirus strain FCoV C1Je Charlotte Dye BVMampS PhD CertSAM MRCVS
Stuart G Siddell BSc(Hons) PhD
bull This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV) Viral RNAs isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP) derived 100 nucleotide identity
Feline Coronavirus serotypes I and II were reported in natural infection
bull Feline coronavirus serotypes 1 and 2 seroprevalence and association with disease in Switzerland
bull Clin Diagn Lab Immunol October 200512(10)1209-15 bull Maya Kummrow1 Marina L Meli Michael Haessig Enikoe Goenczi Amy Poland Niels C
Pedersen Regina Hofmann-Lehmann Hans Lutz
bull Comparison of serologic techniques for the detection of antibodies against feline coronaviruses
bull J Vet Diagn Invest January 200820(1)45-50 bull Annamaria Pratelli1
bull Prevalence of Korean cats with natural feline coronavirus infections bull Virol J January 20118(0)455 bull Dong-Jun An1 Hye-Young Jeoung Wooseog Jeong Jee Yong Park Myoung-Heon Lee Bong
Kyun Park bull 1National Veterinary Research and Quarantine Service Anyang Kyunggi-do430-824 Korea
bull Moreshellip
Take home message Knowing ME knowing YOU
My team my world
Thank you
J Gen Virol 2010 Feb91(Pt 2)415-20 doi 101099vir0016485-0 Epub 2009 Nov 4
Feline infectious peritonitis insights into feline coronavirus
pathobiogenesis and epidemiology based on genetic analysis of the viral
3c gene Chang HW1 de Groot RJ Egberink HF Rottier PJ
helliphellipMost cats with FIP had no detectable intestinal feline coronaviruses (FCoVs) and
had seemingly cleared the primary FECV infection In those with detectable intestinal
FCoV the virus always had an intact 3c and seemed to have been acquired by FECV
superinfection Apparently 3c-inactivated viruses replicate not at all--or only poorly--in the
gut explaining the rare incidence of FIP outbreaks
FIP transmission
FIP transmission
bull Vet Res 2013 Jul 174457 doi 1011861297-9716-44-57
bull An outbreak of feline infectious peritonitis in a Taiwanese shelter epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus
bull Wang YT1 Su BL Hsieh LE Chueh LL
bull Abstract
bull helliphellipSequence analysis revealed that the type II FIPV detected from fecal samples body
effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death Taken together our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment
FCoV field strain in FIP cat
Genomic RNA sequence of feline coronavirus strain FCoV C1Je Charlotte Dye BVMampS PhD CertSAM MRCVS
Stuart G Siddell BSc(Hons) PhD
bull This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV) Viral RNAs isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP) derived 100 nucleotide identity
Feline Coronavirus serotypes I and II were reported in natural infection
bull Feline coronavirus serotypes 1 and 2 seroprevalence and association with disease in Switzerland
bull Clin Diagn Lab Immunol October 200512(10)1209-15 bull Maya Kummrow1 Marina L Meli Michael Haessig Enikoe Goenczi Amy Poland Niels C
Pedersen Regina Hofmann-Lehmann Hans Lutz
bull Comparison of serologic techniques for the detection of antibodies against feline coronaviruses
bull J Vet Diagn Invest January 200820(1)45-50 bull Annamaria Pratelli1
bull Prevalence of Korean cats with natural feline coronavirus infections bull Virol J January 20118(0)455 bull Dong-Jun An1 Hye-Young Jeoung Wooseog Jeong Jee Yong Park Myoung-Heon Lee Bong
Kyun Park bull 1National Veterinary Research and Quarantine Service Anyang Kyunggi-do430-824 Korea
bull Moreshellip
Take home message Knowing ME knowing YOU
My team my world
Thank you
FIP transmission
bull Vet Res 2013 Jul 174457 doi 1011861297-9716-44-57
bull An outbreak of feline infectious peritonitis in a Taiwanese shelter epidemiologic and molecular evidence for horizontal transmission of a novel type II feline coronavirus
bull Wang YT1 Su BL Hsieh LE Chueh LL
bull Abstract
bull helliphellipSequence analysis revealed that the type II FIPV detected from fecal samples body
effusions and granulomatous tissue homogenates from the cats that succumbed to FIP all harbored an identical recombination site in their S gene Two of the cats that succumbed to FIP were found to harbor an identical nonsense mutation in the 3c gene Fecal shedding of this type II virus in the effusive form of FIP can be detected up to six days before death Taken together our data demonstrate that horizontal transmission of FIPV is possible and that FIP cats can pose a potential risk to other cats living in the same environment
FCoV field strain in FIP cat
Genomic RNA sequence of feline coronavirus strain FCoV C1Je Charlotte Dye BVMampS PhD CertSAM MRCVS
Stuart G Siddell BSc(Hons) PhD
bull This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV) Viral RNAs isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP) derived 100 nucleotide identity
Feline Coronavirus serotypes I and II were reported in natural infection
bull Feline coronavirus serotypes 1 and 2 seroprevalence and association with disease in Switzerland
bull Clin Diagn Lab Immunol October 200512(10)1209-15 bull Maya Kummrow1 Marina L Meli Michael Haessig Enikoe Goenczi Amy Poland Niels C
Pedersen Regina Hofmann-Lehmann Hans Lutz
bull Comparison of serologic techniques for the detection of antibodies against feline coronaviruses
bull J Vet Diagn Invest January 200820(1)45-50 bull Annamaria Pratelli1
bull Prevalence of Korean cats with natural feline coronavirus infections bull Virol J January 20118(0)455 bull Dong-Jun An1 Hye-Young Jeoung Wooseog Jeong Jee Yong Park Myoung-Heon Lee Bong
Kyun Park bull 1National Veterinary Research and Quarantine Service Anyang Kyunggi-do430-824 Korea
bull Moreshellip
Take home message Knowing ME knowing YOU
My team my world
Thank you
FCoV field strain in FIP cat
Genomic RNA sequence of feline coronavirus strain FCoV C1Je Charlotte Dye BVMampS PhD CertSAM MRCVS
Stuart G Siddell BSc(Hons) PhD
bull This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV) Viral RNAs isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP) derived 100 nucleotide identity
Feline Coronavirus serotypes I and II were reported in natural infection
bull Feline coronavirus serotypes 1 and 2 seroprevalence and association with disease in Switzerland
bull Clin Diagn Lab Immunol October 200512(10)1209-15 bull Maya Kummrow1 Marina L Meli Michael Haessig Enikoe Goenczi Amy Poland Niels C
Pedersen Regina Hofmann-Lehmann Hans Lutz
bull Comparison of serologic techniques for the detection of antibodies against feline coronaviruses
bull J Vet Diagn Invest January 200820(1)45-50 bull Annamaria Pratelli1
bull Prevalence of Korean cats with natural feline coronavirus infections bull Virol J January 20118(0)455 bull Dong-Jun An1 Hye-Young Jeoung Wooseog Jeong Jee Yong Park Myoung-Heon Lee Bong
Kyun Park bull 1National Veterinary Research and Quarantine Service Anyang Kyunggi-do430-824 Korea
bull Moreshellip
Take home message Knowing ME knowing YOU
My team my world
Thank you
Feline Coronavirus serotypes I and II were reported in natural infection
bull Feline coronavirus serotypes 1 and 2 seroprevalence and association with disease in Switzerland
bull Clin Diagn Lab Immunol October 200512(10)1209-15 bull Maya Kummrow1 Marina L Meli Michael Haessig Enikoe Goenczi Amy Poland Niels C
Pedersen Regina Hofmann-Lehmann Hans Lutz
bull Comparison of serologic techniques for the detection of antibodies against feline coronaviruses
bull J Vet Diagn Invest January 200820(1)45-50 bull Annamaria Pratelli1
bull Prevalence of Korean cats with natural feline coronavirus infections bull Virol J January 20118(0)455 bull Dong-Jun An1 Hye-Young Jeoung Wooseog Jeong Jee Yong Park Myoung-Heon Lee Bong
Kyun Park bull 1National Veterinary Research and Quarantine Service Anyang Kyunggi-do430-824 Korea
bull Moreshellip
Take home message Knowing ME knowing YOU
My team my world
Thank you
Take home message Knowing ME knowing YOU
My team my world
Thank you
My team my world
Thank you