hepatitis viruses
DESCRIPTION
Hepatitis Viruses. Fe A. Bartolome, MD Department of Microbiology Our Lady of Fatima University. HEPATITIS A. infectious hepatitis; Enterovirus 72 Picornavirus genus Heparnavirus/Hepatovirus naked, icosahedral symmetry positive sense, ssRNA virus with a VPg protein attached to 5” end - PowerPoint PPT PresentationTRANSCRIPT
Fe A. Bartolome, MD
Department of Microbiology
Our Lady of Fatima University
HEPATITIS A
• infectious hepatitis; Enterovirus 72
• Picornavirus genus Heparnavirus/Hepatovirus
• naked, icosahedral symmetry
• positive sense, ssRNA virus
• with a VPg protein attached to 5” end
• replication similar to other Picornaviruses
• not cytolytic
• released by exocytosis
HEPATITIS A
Characteristics:
Stable to: acid (pH 1), solvents (ether, chloroform), detergents, salt/ground water, drying, temperature (40C – 560C)
Inactivated by: chlorine treatment, formalin, UV radiation
HEPATITIS A
Pathogenesis:
MOT: fecal-oral food (shellfish – clams, oysters, mussels); water; dirty hands
Ingestion oropharynx or epithelial lining of intestines blood stream liver (hepatocytes and Kupffer cells) bile stool
Virus shedding: 2-3 wks before & 1 week after onset of jaundice or until antibody is detected
Interferon – limits viral shedding
NK cells & cytotoxic T cells lysis of infected cells
Antibody, complement, ADCC induce immunopathology
HEPATITIS A
Pathogenesis:
MOT: fecal-oral food (shellfish – clams, oysters, mussels); water; dirty hands
Ingestion oropharynx or epithelial lining of intestines blood stream liver (hepatocytes and Kupffer cells) bile stool
Virus shedding: 2-3 wks before & 1 week after onset of jaundice or until antibody is detected
Interferon – limits viral shedding
NK cells & cytotoxic T cells lysis of infected cells
Antibody, complement, ADCC induce immunopathology
HEPATITIS A
Epidemiology:
90% of infected children & 20-25% of infected adults with inapparent but productive infections
HAV viremia transient blood-borne transmission rare
HEPATITIS A
Clinical Syndromes:
Children: mild infection, usually asymptomatic
Adults: abrupt onset of symptoms
viral shedding precedes onset of symptoms
complete recovery in 99%
fulminant hepatitis: 1-3 persons/1000 with 80% mortality
immune complex-related symptoms rare
HEPATITIS A
Laboratory Diagnosis:
ELISA or radioimmunoassay
(+) IgM anti-HAV acute infection fecal shedding decreases as IgM titer increases
(+) IgG anti-HAV resolution, past infection
Prophylaxis: immune serum globulin < 2 wks after exposure
HEPATITIS B
serum hepatitis
Hepadnavirus
infects liver, kidneys and pancreas humans and chimpanzees
15% of population infected during birth or childhood
small, enveloped
circular, partly ds DNA virus
mature virion Dane particle
HEPATITIS B
Important proteins:
1. DNA polymerase – with reverse transcriptase & ribonuclease H activity
2. HBcAg – core antigen; surrounds polymerase; T cell antigens
3. HBeAg – minor component of virion; primarily secreted into serum
4. HBsAg – surface antigen; Australia antigen
5. HBx – transcriptional transactivator; promote viral replication; protein kinase
HEPATITIS B
HBsAg with 3 glycoproteins encoded by same gene but translated from different AUG start codons
1. S (gp27) – contained in M glycoprotein; major component of HBsAg
2. M (gp36) – contained in the L glycoprotein
3. L (gp42) – essential for virion assembly
HEPATITIS B
Replication unique:
1. With distinctly defined tropism for liver
2. Small genome economy in transcription and translation
3. Replicates through an RNA intermediate
Binds to human serum albumin target the virus to the liver
Cell penetration partial DNA strand converted to complete dsDNA nucleus
HEPATITIS B
two phases of hepatocyte infection:
1. Proliferative phase
HBV DNA present in episomal form
Viral HBsAg & HBcAg + MHC class I molecules activation of CD8+ T cells (+) hepatocyte destruction
2. Integrative phase
For hepatocytes not destroyed by immune system viral DNA incorporated into host genome
HEPATITIS B
(+) HBsAg and HBeAg in blood on-going active infection
MOT:
1. Blood & other body fluids – semen, saliva, milk, vaginal secretions, amniotic fluid
2. Sexual contact
3. Perinatal – passage through birth canal
Intracellular accumulation of filamentous forms of HBsAg responsible for characteristic ground glass cytopathology
HEPATITIS B
CMI + inflammation responsible for causing symptoms; eliminate infected hepatocytes
Immune complexes between HBsAg and anti-HBs (+) type III HS reaction vasculitis, arthralgia, rash, renal damage
Infants & young children immarture CMI less ability to resolve infection 90% chronic carriers
HEPATITIS B
Spread of Hepatitis B
MOT Blood
Liver
Prevent spread & disease
Ab
Ab
HBsAg
Symptoms, resolution
Viremia
Immune complex
Type III HS
CMI
HEPATITIS B
Clinical outcomes:
Acute Hepatitis B
Resolution Fulminant
HBsAg+ > 6 months
Resolution Asymptomatic carrier state
Chronic persistent hepatitis
Chronic active hepatitis
Extrahepatic disease: PAN, GN
Cirrhosis HCC
90%
9%
1%
50%
HEPATITIS B
Laboratory:
Detection of HBeAg is the best correlate to the presence of infectious virus
Chronic infection continued finding of HBeAg, HBsAg or both without detectable antibodies
HEPATITIS B
Interpretation of Serologic Markers of HBV Infection
Serologic reactivity
Pre- symptoms
Early Acute Acute Chronic
Late acute Resolved
Vacci-nated
Anti-HBc
Anti-HBe
Anti-HBs
HBeAg
HBsAg
Infectious virus
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HEPATITIS C
NANB post-transfusion hepatitis
Flavivirus genus Hepacivirus
Enveloped, ss positive sense RNA virus
5’ end encodes nucleocapsid core protein highly conserved
Envelope proteins E1 and E2
Hypervariable regions (HVR1 & 2) present in E2 sequence
Non-structural proteins (e.g. NS5B viral RNA-dependent RNA polymerase) with poor fidelity
HEPATITIS C
Infects only humans and chimpanzees
Binds to cells with CD81 surface receptors OR coats itself with LDL or VLDL & uses their receptors for uptake into hepatocytes
Inhibit apoptosis & IFN- by binding to TNFR and protein kinase R (PKR) prevent death of host cell and promote persistent infection
CMI production of tissue damage
Antibody not protective
HEPATITIS C
Remains cell-associated
MOT:
1. Parenteral - >90% of HIV (+) individuals infected with HCV
2. Secretions
3. Sexual
4. Perinatal (6%)
PERSISTENT INFECTION AND CHRONIC HEPATITIS ARE THE HALLMARKS!
HEPATITIS C
Outcomes:
HCV Acute infection
Recovery & clearance Persistent infection
Chronic hepatitis
Liver failure Cirrhosis HCC
HEPATITIS C
Laboratory:
(+) anti-HCV antibodies (50-70%) in symptomatic acute infection
HCV RNA persists despite presence of neutralizing antibodies (90%)
Episodic elevation of serum aminotransferases
Treatment: IFN- alone or with ribavirin – only known treatment
HEPATITIS D
Delta hepatitis; viroid-like
Replication defective viral parasite
Enveloped, circular RNA virus surrounded by delta antigen core surrounded by HBsAg-containing envelope
Unusual transcription and replication process
Host cell RNA pol II makes RNA copy replicates genome makes mRNA form a ribozyme cleave RNA circle form mRNA
HEPATITIS D
MOT similar to HBV
Replicate and cause disease only in people with active HBV infection results in cytotoxicity and liver damage
With direct cytopathic effect
HEPATITIS D
Clinical outcomes: Co-infection
HDV + HBV
Healthy individual
Fulminant hepatitis
Recovery w/ immunity
Chronic HBV/HDV hepatitis
Cirrhosis Death
90% rare3-4%
HEPATITIS D
Clinical outcomes: Superinfection
HDV
HBV carrier
Fulminant hepatitis
Acute, severe disease
Chronic HBV/HDV hepatitis
Cirrhosis Death
10-15% 80%7-10%
Recovery
HEPATITIS E
Enteric or epidemic NANB hepatitis
MOT: fecal-oral
Resembles Calicivirus or Norwalk agent in size and structure non-enveloped, ssRNA virus
Symptoms and course similar to HAV
Causes only acute disease
Poor response to serum IgG
Infection serious in pregnant women mortality approx. 20%
HEPATITIS G
Flavivirus similar to HCV
MOT: contaminated blood or blood products; possibly sexual
In 75% of infection HGV cleared from plasma; 25% become chronic
Site of replication: mononuclear cells not hepatotropic
Does not cause elevation in serum aminotransferases
With protective effect on patients co-infected with HIV inhibit HIV replication in cultures of peripheral blood mononuclear cells