1. Hepatitis Viruses Chapter 35

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 Risk of infection is very low in N. America, Europe, Australia 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.

6. 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

7. 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)

8. 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 Hepatitis Virus Infections in Humans

9. 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