the minus sense and ambisense rna viruses there are 7 families of minus strand rna viruses all minus...
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The Minus Sense and Ambisense RNA Viruses
There are 7 families of minus strand RNA viruses
All minus strand RNA viruses are enveloped with helical nucleocapsids. Families may differ in morphology of the virion, however.
No polyproteins are made and the viruses do not encode proteases.
Because the viral genomes are not mRNAs, all must contain enzymes within the virion to synthesize mRNA.
Four families have a single piece of RNA as their genome and are grouped into the order Mononegavirales. The remaining three familes have segmented genomes.
Minus strand or ambisense viruses infect vertebrates or plants. Some are arboviruses and thus infect arthropods as well.
All RNA synthesis takes place within nucleocapsids. The genome is never released free into the cytoplasm.
NEGATIVE STRAND RNA VIRUSES
Orthomyxoviridae
Bunyaviridae
FAMILY/ GENUS
HOST(S) TRANSMISSION
MONONEGAVIRALES (NONSEGMENTED NEGATIVE STRAND VIRUSES)Rhabdoviridae
Filoviridae
Paramyxoviridae
SEGMENTED NEGATIVE STRAND RNA VIRUSES
Two genera of plant viruses
GENOME SIZE TYPE VIRUS
Vertebrates Some arthropod-borneVesiculovirus VSIVLyssavirus Contact with salivaVertebrates RabiesEphemerovirus Arthropod-borneCattleBEFVNovirhabdovirus FishIHNV
13-16
13
16-20
Vertebrates “Marburg-like viruses” Marburg
13 in 8 segments
Respirovirus Sendai AirborneVertebrates
11-20 in 3 segments
ArenaviridaeVertebrates
10-14 in 2 segmentsArenavirus LCMV
Morbillivirus Measles AirborneVertebratesRubulavirus Mumps AirborneVertebrates
AirborneMegamyxovirus Hendra VertebratesPneumovirus HRSV AirborneVertebrates
Vertebrates Bunyavirus Bunyamwera Mosquito-borneHantavirus Hantaan Vertebrates Feces/urine/salivaNairovirus Dugbe Vertebrates Tickborne
Arthopod-bornePhlebovirus Rift Valley fever Vertebrates Tospovirus TSWV Plants Thrips
Urine/saliva
Metapneumovirus TRTV Turkeys Airborne
Influenzavirus C AirborneInfluenza C Vertebrates
Bornaviridae ~9 BDV Vertebrates Bornavirus
“Ebola-like viruses” Zaire Ebola virus Vertebrates
Vertebrates Influenzavirus A Airborne Influenza A Influenzavirus B Influenza B Vertebrates Airborne
Arthropod-borne
Thogotovirus Thogoto Vertebrates Arthropod-borne
( in kb)
3' 5'
RUBULAVIRUS
MONONEGAVIRALES
PB1RNA5 RNA8 RNA7
ORTHOMYXOVIRIDAE
N NS1/NS2 M1/M2 NAHA
PB2 PA
Nucleocapsid Genes Glycoprotein Gene(s) Polymerase Gene(s)
SEGMENTED
BUNYAVIRIDAE
N G2 NSm
S RNA M RNA L RNA
L BUNYAVIRUS
ARENAVIRIDAE S RNA L RNA
L ARENAVIRUSN G2 G1
RNA4 RNA 1 RNA 3RNA2RNA6
(SSHV)
(LCMV)NS
(FLUAV)
BORNAVIRIDAE
le N P M G L BORNAVIRUS(BDV)
tr
FILOVIRIDAE
le FILOVIRUS(ZEBOV)
N P M1 GP LM2p30tr
le N P M G
RHABDOVIRIDAEVESICULOVIRUS
(VSIV)L tr
PARAMYXOVIRIDAE
P/V F HN(SV-5)
MN LSHle tr
NSs
NSs
G1
INFLUENZAVIRUS A
RHABDOVIRIDAE
VESICULOVIRUS
LYSSAVIRUSRabies
EPHEMEROVIRUS
Worldwide, except Australia, PNG, and Antarctica
Africa, Asia, Australia,
CYTORHABDOVIRUS
Humans, dogs, skunks, foxes, raccoons
Adelaide River virus
Berrimah virus
Lettuce necrotic yellows Northern cereal mosaicStrawberry crinkle
NUCLEORHABDOVIRUS
AphidsLeafhopperAphid
Potato yellow dwarf LeafhopperMaize mosaic Leafhopper
Sonchus yellow net Aphid
Cattle, water buffalo
Hematophagous arthropods
Infectious saliva
Fever, anorexia
Malaise, then delirium, then coma and death
PlantsPlantsPlants
Plants
Plants
Plants
Bovine ephemeral fever
Europe, Africa, Australia
Bat lyssaviruses Bats, humans
Like rabies
Vesicular stomatitis Indiana
AmericasHumans, horses, ruminants, swine
Vesicles on tongue and lips
Airborne,Insects?
Mokola AfricaHumans, dogs, cats, shrews
Like rabies?
GENUS/ MEMBERS
USUAL HOST(S)
TRANSMISSION/ VECTOR?
DISEASE WORLD DISTRIBUTION
Piry Mice, humans
BrazilFebrile illnessSandflies
India, Asia?Chandipura Sandflies Febrile illnessMammals including humans
Infectious saliva
NOVIRHABDOVIRUSSalmonid fish Pacific Northwest
of N. A.HemorrhageInfectious
hematopoietic necrosis (and other fish viruses)
?
Vesicular Stomatitis Virus
Nucleocapsids
of
(-)RNA
Viruses
Schematic Diagram of a Rhabdovirus
G
M
NS
N
RNA
L
Lipid Bilayer
le N P M G L tr
SIE3’ 5’
Genome RNA
G mRNAM mRNA
...AUAGGGAUACUUUUUUUGAUUGUCUCUAG...5’ 3’Gppp
m
AACAGAGAUC......UAUCCCUAUG poly(A)
A. Location of intergenic sequences of VSV (a rhabdovirus), and detailed view of the M/G intergenic region
B. Genomic sequences at other intergenic regions in the VSV genome3’ 5’
N/P ...CGAUGUAUACUUUUUUUGAUUGUCUAUAG...P/M ...CAUCUGAUACUUUUUUUCAUUGUCUAUAG...G/L ...UUAAAAAUACUUUUUUUGAUUGUCGUUAG...
mRNAS
Diagram of the VSV Genome and the Structure of the Gene Junctions
Replication of Rhabdovirus RNA
Switch from mRNA synthesis to RNA replication occurs when sufficient N protein has been made to encapsidate the newly synthesized RNA.
The (+)RNA is then encapsidated during synthesis and a perfect complementary copy of the genome is produced. Stop signals, poly(A) signals, reinitiation signals are all ignored.
The encapsidated antigenomic RNA can be used in turn to synthesize more genomic RNA
Synthesis of genomic (-)RNA also requires encapsidation of the newly synthesized RNA during synthesis.
Thus, protein synthesis is required for replication of the genome but not for synthesis of mRNAs.
Genomic RNA and antigenomic templates are never free but are always present in nucleocapsids, whereas mRNAs are not encapsidated.
Budding VSV
Rabies VirusThe most dangereous rhabdovirus is rabies virus and its ally bat lyssavirus
The virus is associated with wildlife--it is a zoonotic virusThe virus is usually transmitted to humans by the bite of a rabid animal--
there is no human-to-human transmission
The virus first replicates around the site of the bite
The probability of CNS infection depends upon the location of the bite
Once the symptoms of rabies occur the infection is uniformly fatal
Louis Pasteur developed an early vaccine against rabies
50,000 humans die each year of rabies
A modern vaccine is widely used to prevent rabies
One million people are inoculated each year following exposure
Because transfer to the brain in delayed, the vaccine can be administered postexposure
Transmission to the CNS may occur upon infection of axons near the site
Bats are an important reservoir. Transmission to humans from bats may sometimes occur through aerosols.
2000199019801970196019501940
10
20
30
40
50
60
Year
10,000
8000
6000
4000
2000DEATHSCASES
Human Rabies
Dogs
Wildlife
Nu
mb
er o
f H
um
an D
eath
s (c
ases
) p
er Y
ear
Nu
mb
er o
f A
nim
al C
ases
per
Yea
r
Rabies in the United States, 1940-1995
Ohio
North Carolina
Virginia
Pennsylvania
New York
Maine
New Hampshire
Massachusetts
Rhode Island
New Jersey
Connecticut
DelawareMaryland
Vermont
1977-1979
1980-1984
1985-1989
1990-1994
1994-1998
No raccoon rabies detected
West Virginia
Spread of Raccoon Rabies throughout the Atlantic Seaboard
Control of Rabies by Vaccination of Wildlife
Wildlife in areas of the U.S. and Europe have been vaccinated using baits containing vaccine.
The bait contains attenuated rabies virus or contains vaccinia virus that expresses rabies G protein.
The bait is often broadcast from planes.
Such programs have been moderately successful in containing the spread of rabies, but are expensive and manpower-intensive.
ParamyxovirusesParamyxoviruses have genomes of 15-20 kb and have 8-11 (or more) genes
Six genera are currently recognized
The family contains many important human pathogens
Many viruses cause respiratory disease including pneumonia
Mumps virus and measles virus are paramyxoviruses
Transmission of the viruses is by aerosols
To date, only mammals and birds are known to be infected by paramyxoviruses
Two recently identified viruses cause encephalitis in humans
Many are specific for a particular host
Many of the human viruses infect only humans
Virions are usually spherical when grown in culture, but clinical specimens are often filamentous
PARAMYXOVIRIDAE
RESPIROVIRUSHuman parainfluenza 1,3
Airborne WorldwideHumans Respiratory disease
Sendai Mice Worldwide
Worldwide
Paramyxovirinae
Bovine parainfluenza 3
MORBILLIVIRUSMeasles
Distemper Dogs, marine mammals
Worldwide
Rinderpest
Humans, monkeys
PneumovirinaePNEUMOVIRUSHuman respiratory syncytial
Humans
Bovine respiratory syncytial
Cattle
Pneumonia virus of mice
Mice
Turkeys
RUBULAVIRUSMumps Humans
Human parainfluenza 2, 4a, 4bSimian virus 5
Parotitis, orchitis, meningitis
Worldwide
Fever, rash, SSPE, immune suppression
Cattle, swine Gastroenteritis
Immune suppression, gastroenteritis, CNS disease
Worldwide
Monkeys, canines
Cattle, sheep
Respiratory distress, diarrhea
Gallinaceous birds
Worldwide
Newcastle disease ,
Worldwide
Worldwide
Worldwide
Worldwide
Worldwide
Worldwide
Worldwide
METAPNEUMOVIRUS
MEGAMYXOVIRUS Hendra (equine morbillivirus)
Humans, equines, Pteropus fruit bats
AustraliaRespiratory disease, encephalitis
Body fluids?
Nipah Humans, swine, cats, dogs
Malaysia, Singapore
GENUS/ MEMBERS
USUAL HOST(S)
TRANSMISSION DISEASE WORLD DISTRIBUTION
Airborne
Airborne
Airborne
Airborne
Airborne
Airborne
Airborne
Airborne
Airborne
Humans
Turkey rhinotracheitis
Respiratory disease, encephalitis
Body fluids?
Airborne
Airborne
Airborne
Airborne
Respiratory diseaseRespiratory disease
Respiratory diseaseRespiratory disease
Respiratory diseaseRespiratory diseaseRespiratory disease
Respiratory disease
SV5
Negative strain Sectioned
Measles virus
SV5
Budding Filamentous Form of SV5
Figure 4.6
genome (kb)
161086420 18
Genome Organizations of Five Genera of theParamyxoviridae.
RESPIROVIRUSHPIV-315462 nt2258572539353603515
LHNFMP/CNaa
RUBULAVIRUSSV-5
15246 nt510 392 529377
SH
44 565 2255N V/P M F HN L
aa
MORBILLIVIRUSMeV
15894 ntL
2183 N 525
P507
M335 553
F H617aa
MEGAMYXOVIRUS (Hendra virus, 18234nt)
N532
P/V/C707 546
FM352
G604
L2244 aa
PNEUMOVIRUS HRSV
15225ntNS1NS2
139124
N391
P241
M256 65
G299 574
F M2195/90
L2166
SH
aa
3’ 5’
MEASLESMORBILLIVIRUS
HPIV-2, HPIV-4, SV-5, (NDV)
SENDAI
HPIV- 3
MUMPS
HPIV- 1 C protein
P protein
C proteinP protein
V protein+ 1 G
RESPIROVIRUS
RUBULAVIRUS
ORF1 ORF2 ORF3 Cysteine-rich domain
C proteinP protein
V protein+ 1 G
* **** *
V protein
+ 4G I protein
+ 2G P protein
* **** *
V protein+ 2G
P protein
* **** *
C proteinP protein
D protein+ 2G
V protein+ 1 G
* **** *
* **** *
MEGAMYXOVIRUSNIPAH
* **** *
P proteinC protein
V protein+ 1 G
****
Translation Strategy of the P Gene of Paramyxoviruses
Pneumovirinae
Paramyxovirinae
Subfamily
Pneumovirus Metapneumovirus
Genus Species 100 nt substitutions
NDV HPIV-2
SV-5 MuV
HPIV-4a HPIV-4b
HPIV-1 SeV
HPIV-3 CDV PDV
RPV MeV
PPRV DMV
TRTV HRSV
Respirovirus
Morbillivirus
Megamyxovirus Hendra Nipah
Rubulavirus
Phylogenetic Tree of the Paramyxoviridae (Derived from the sequences of the N ORF)
Measles virus
Measles virus was once epidemic throughout the world. Very few people escaped infection by it.
It is spread by aerosols and begins infection in the URT. It then becomes systemic and infects many organs.
It causes a serious illness. It leads to temporary suppression of the immune system and infected persons may succumb to secondary infectionn.Infection of the CNS can lead to neurological sequella, including SSPE.
A live vaccine, part of the MMR vaccine, has almost eradicated measles from the Americas. The virus is still epidemic in Africa and parts of Asia, however, and imported cases have resulted in small epidemics in the U.S.
Worldwide 2.5 million/year died from measles.
Measles Virus History
Measles virus is a human virus and humans are the only reservoir in nature.
Infection results in solid, life-long immunity.
Spread is by direct person-to-person contact.
Therefore a minimum population size of about 500,000 is required to maintain the virus, and measles could not have existed before human populations reached this size.
This may have occurred about 5000 years ago following domestication of plants and animals.
When the virus was first introduced into naïve populations during European exploration 200-500 years ago, the death toll was enormous. One result, aided by smallpox, was the depopulation of the Americas.
20
15
10
5
01 2 3 4 5 6 70
Iceland
New HebridesNew CaledoniaSolomon Islands
French Polynesia
Tonga
Western Samoa
Mean Distance Between New Susceptibles (Kilometers)
Du
rati
on
of
Ep
idem
ics
of
Measl
es
(Mon
ths)
B.
100
80
60
40
20
04 8 12 16
Guam
Bermuda
A.
New Susceptibles in Thousands per Year
Perc
en
t of
Mon
ths
wit
h C
ase
s of
Measl
es
Effect of Population Size and Density on the Epidemiology of Measles
Measles vaccine licensed
1982 1987 1992 1997Rep
orte
d C
ases
(th
ousa
nd
s)
Rep
orte
d C
ases
(th
ousa
nd
s)
30
20
10
0
1962 1967 1972 1977 1982 1987 1992 1997
500
450
400
350
300
250
200
150
100
50
0
Cases of Measles in the United States, 1962 to 1997
5 10 15 20 25 30 35 40Age (Months)
EZ-HT
SW-HT
Standard
Mort
ali
ty (
per
10
00
ch
ild
ren
at
5 m
on
ths)
200
150
100
50
0
Trial in Senegal with High-Titer Measles Vaccine
Rep
ort
ed
case
s /1
00
,00
0 p
op
ula
tion
Mumps vaccine licensed in 1967
1968 1972 1976 1980 1984 1988 1992 1996
1982 1987 1992 1997
76
54
32
10
Rep
ort
ed
case
s /1
00
,00
0 p
op
ula
tion 90
80
70
60
50
40
30
20
10
0
Incidence of Mumps in the United States, 1968-1998
Respiratory Syncytial Virus
RSV is the leading cause of pneumonia in infants worldwide.
Infection begins in the URT but spreads to the LRT in ~1/3 of primary infections.
Immunity following infection is incomplete and children and adults suffer recurrent infections.
Disease symptoms are usually milder in second and subsequent infections, however.
RSV infection of immunocompromised persons is very serious.
No vaccine exists. Clinical trials with an inactivated virus vaccine gave the disastrous result that vaccinated individuals suffered more serious illness upon subsequent infection by RSV.
VIRUSES CAUSING RESPIRATORY DISEASE
Family Virus Nucleic Acid Host Range
RSV = respiratory syncytial virus; NDV = Newcastle disease virus; HCoV = human coronavirus; IBV = infectious bronchitis virus; CLTV = canine laryngotracheitis; EBV = Epstein-Barr virus.
Adapted from Tables of Respiratory Viruses pp 1493,1494 in the Encyclopedia of Virology.
Disease(s)
Picornaviridae ss plus strand RNA
HumansRhinoviruses Common cold (rhinitis), pharyngitis
Coxsackie A Humans Rhinitis, pharyngitis
Coronaviridae ss plus strand RNA
HCoV Humans RhinitisIBV Fowl Bronchitis
OrthomyxoviridaeInfluenza ss minus strand RNA
Humans, birds, horses, swine
Rhinitis, pharyngitis, croup, bronchitis, pneumonia
Paramyxoviridae RSV ss minus strand RNA
Humans, cattle Rhinitis, pharyngitis, croup, bronchitis, pneumonia
Human parainfluenza
Humans Rhinitis, pharyngitis, croup, bronchitis, pneumonia
Measles Humans Pneumonia
Canine distemper Dog Bronchitis, pneumoniaBirdsNDV Respiratory distress
Caliciviridae Feline calicivirusss plus strand RNA
Cats Rhinitis, tracheitis, pneumonia
Herpesviridae Cytomegalovirus Humans Pharyngitis, pneumoniads DNAHerpes simplex, EBV, varicella
Humans Pharyngitis, pneumonia
Various alphaherpesvirinae
Cattle, cat, horse, chicken
Rhinotracheitis
Adenoviridae Human Ad40,41 ds DNA Humans Rhinitis, pharyngitis, pneumoniaCLTV Dog Pharyngitis, tracheitis, bronchitis,
and bronchopneumonia
Hendra Virus and Nipah Virus
Hendra virus first appeared in Australia in 1994
Associated with an outbreak of equine respiratory disease
Three humans became ill from the virus, two of whom died.
Nipah virus first appeared in 1998 in Malaysia and Singapore.
Causative agent of an epidemic of human encephalitis
258 cases occurred with 40% mortality rate
Associated with pigs, which served as amplifying hosts
These two viruses are related and flying foxes are now known to be the reservoir
They represent emerging viruses that were previously unknown but suddenly appeared to cause serious human illness
Filoviridae
MARBURG-LIKE VIRUSESMarburg
Reston Ebola
Sudan Ebola
Zaire Ebola
Humans
Humans
Cynomolgus monkeys
Contact with bloodor other body fluids
*Natural reservoirs unknown
AfricaSevere hemorrhagicdisease
Severe hemorrhagic disease in monkeys, attenuated in man
Philippines
Contact with bloodor other body fluids
Severe hemorrhagicdisease
Africa
EBOLA-LIKE VIRUSES
Cote d’Ivoire Ebola
*GENUS/
MEMBERSUSUAL HOST(S)
TRANSMISSION DISEASE WORLD DISTRIBUTION
VIRUS NAMEABBREV.
MARV
SEBOV
ZEBOV
CIEBOV
REBOV ?
Filovirus Virions
Marburg Virus Ebola Zaire Virus
200 nm 200 nm
Filovirus Outbreaks
Marburg
Ebola
Year Cases/ %Mortality
Year Cases/ %Mortality
1975 3 (33%) Zimbabwe1980 2 (50%) Kenya1987 1 (0%) Kenya
1976 284 (53%) Sudan
1994 44 (64%) Gabon1994 1 (0%) Ivory Coast
1995/9637 (57%) Gabon1996/97 60 (75%) Gabon
1998/0099 (80%) Zaire*
*Now called Democratic Republic of Congo
*1977 1 (100%) Zaire1976 318 (88%) Zaire
*
1995 315 (77%) Zaire (Kikwit)*
Sudan
GabonKenya
Zaire*
Zimbabwe
•1980•1987
•1975
•1976•1979
Ivory Coast
•1976
•1994•1995/96•1996/97
•1995
•1994
•1998/00
•1977
1979 34 (65%) Sudan
Uganda•2000
2000 425 (53%) Uganda
Country
Country
30201000
100
200
300
400
500
Ebola Epidemic in Uganda - October 2000 through January 2001
Cu
mu
lati
ve To
tals
Cases
Deaths
October 10 20November
10 20December Jan.
Borna Disease Virus
Borna disease virus is a (-)RNA virus of 9 kb.
Originally known as a pathogen of horses and sheep, it probably infects all warm blooded vertebrates.
Where known, it infects the CNS and produces only small amounts of virus.
It is associated with abnormalities in movement and behavior.
In horses, the disease may ameliorate or may progress to paralysis and death.
Infection is not cleared by the immune system and becomes chronic.
There is preliminary evidence that the virus may be associated with neurological disease in humans, including schizophrenia and bipolar disease.
Its geographic range is probably worldwide.
Borna Disease Virus
100 nm
Borna Disease Virus Transcription Map
Borna disease virus replicates in the nucleus and many mRNA are spliced