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Hepatitis Viruses

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  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. 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

  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