Transcript Chapter 35 Hepatitis viruses

Hepatitis Viruses
Chapter 35
Properties of Hepatitis Viruses
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Six known
Hepatitis type A virus (Picornaviridae)
Hepatitis type B virus (Hepadnaviridae)
Hepatitis type C virus (Flaviviridae)
Hepatitis type D virus (viroid, unclassified)
Hepatitis type E virus (unclassified)
Hepatitis type G virus (Flaviviridae)
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Properties of Hepatitis Viruses
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Hep A virus
Picornavirus (a picornavirus)
ssRNA, 7.5 kb
One serotype
Nonenveloped
Features
Children, young adults
Fecal-oral transmission
Global distribution
Risk of infection is very low in N. America, Europe,
Australia
Poor sanitation greatest risk factor
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Properties of Hepatitis Viruses
Hep B virus (a hepadnavirus)
ds DNA virus, 3.2 kb
Enveloped
Predominant spike protein is hepatitis B surface antigen
(HBsAg)
Recombinant HBsAg is formulated in vaccine
7 polypeptides
Unusual genome replication
DNA is copied into RNA transcript
Some copies of the RNA transcript are reverse transcribed
into ssDNA
The ssDNA is transcribed into dsDNA
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Properties of Hepatitis Viruses
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Hep C virus (a flavivirus)
Plus-strand RNA, 9.4 kb
Transmission primarily through blood products
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Sexual transmission can occur
Could not be propagated in vitro until very recently
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Reverse genetics was used to produce infectious clones of Hep C
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Copy of vRNA genome into dsDNA
Clone into a plasmid with appropriate promoter
Express in cells to produce viral proteins (yeast) or infectious virus
(mammalian cells)
Most acute infections are subclinical
However, most will develop chronic hepatitis
About 25,000 people die from HCV infection each year in U. S.
Properties of Hepatitis Viruses
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Hep D virus
Minus-strand RNA, 1.7 kb
Not a virus, but a viroid
Requires Hep B coinfection
Substantially contributes to Hep B pathogenesis
Hep E virus
Plus-strand RNA, 7.6 kb
Oral-fecal transmission
High fatality rate in pregnant women (20%)
Hep G virus
Plus-strand RNA, 10 kb
Transmission through blood products
No known disease
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Hepatitis Virus Infections in Humans
Targets the liver
Cause focal necrosis, leading to larger areas of necroses
Jaundice
If recovery occurs, liver function often returns to normal
Substantial damage cannot be reversed
HBV and HCV have been associated with hepatocellular
carcinomas
HBV can cause rash, arthritis, vasculitis and
glomerulonephritis
Fatality Rates
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Hep A: <0.5% (increases after age 40)
Hep B: 1-2% (chronic in 5-10% of infections)
Hep C: 0.5-1% (chronic in 70-90% of infections)
Hepatitis Virus Infections in Humans
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Laboratory Diagnoses
Hep A
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Virus detectable in blood, stool, bile, liver (biopsy)
IgM serology (ELISA)
Hep B
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IgM, IgG serology
PCR
Hep C
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Serology is not useful for discriminating acute or chronic infection
Real-time PCR is assay of choice (viral load)
Hep D
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ELISA to HD antigen
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Virus-Host Immune Reactions
Hep A
Globally, childhood infections are common
In developed countries Hep A is uncommon
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A large susceptible adult population
Childhood vaccination is now routine
Infection results in life-long immunity
Hep B
Health care workers at higher risk
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Hep C
Nothing is known about host immune response to Hep C
No good animal model is available
Only recently has the virus been propagated in cell culture
Treatment
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Type I interferon
Ribavirin