1. Hepatitis Viruses

2. Properties of Hepatitis Viruses
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)

3. Properties of Hepatitis Viruses
Hep A virus
Picornavirus (a picornavirus)
ssRNA, 7.5 kb
One serotype
Nonenveloped
Features
Children, young adults
Fecal-oral transmission
Global distribution
Poor sanitation greatest risk factor

4. 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

5. Properties of Hepatitis Viruses
Hep C virus (a flavivirus)
Plus-strand RNA, 9.4 kb
Transmission primarily through blood products
Sexual transmission can occur
Could not be propagated in vitro until very recently
Reverse genetics was used to produce infectious clones of Hep C
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.

7. Properties of Hepatitis Viruses
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

8. 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
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)

9. Hepatitis Virus Infections in Humans
Laboratory Diagnoses
Hep A
Virus detectable in blood, stool, bile, liver (biopsy)
IgM serology (ELISA)
Hep B
IgM, IgG serology
PCR
Hep C
Serology is not useful for discriminating acute or chronic infection
Real-time PCR is assay of choice (viral load)
Hep D
ELISA to HD antigen

10. Virus-Host Immune Reactions
Hep A
Globally, childhood infections are common
In developed countries Hep A is uncommon
A large susceptible adult population
Childhood vaccination is now routine
Infection results in life-long immunity
Hep B
Health care workers at higher risk
Vaccination is routine
Means of control by immune response is not entirely clear
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
Type I interferon
Ribavirin