Hepatitis VirusesChapter 35

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)

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

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

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.

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

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)

• 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

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