Genes determining the course of virus persistence in the liver: lessons from murine infection with lymphocytic choriomeningitis virus.
More than 500 million people worldwide are persistently infected with either hepatitis B virus (HBV) or hepatitis C virus (HCV). Although both viruses are poorly cytopathic, persistent infection causes severe immunopathologic damage to liver tissue; histologically, such damage is characterized by fatty liver disease, liver fibrosis, and a higher likelihood of hepatocellular carcinoma. Virus-specific CD8+ T cells play a crucial role during infection with hepatitis viruses. On the one hand, rapid activation of CD8+ T cells can control the virus and therefore inhibit its persistence. On the other hand, once the virus persists in the liver, the chronic activation of virus-specific T cells leads to continued liver cell damage. This double-edged role of CD8+ T cells determines the final outcome of infection. In half of cases of human HCV infection, the virus persists; in the other half, the virus is controlled. Additional insights into the molecular mechanisms that determine the course of the disease may be gained from the study of appropriate murine models. This review discusses the similarities and differences between infection with lymphocytic choriomeningitis virus (LCMV) in mice and chronic infection with hepatitis virus in humans.
Lang
Philipp A
PA
Ontario Cancer Institute, Toronto, Ontario, Canada.
Recher
Mike
M
Häussinger
Dieter
D
Lang
Karl S
KS
D000818:Animals; D001117:Arenaviridae Infections / Q000235:genetics* / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016174:Hepacivirus / Q000276:immunology; D006515:Hepatitis B virus / Q000276:immunology; D006521:Hepatitis, Chronic / Q000235:genetics / Q000276:immunology; D006524:Hepatitis, Viral, Animal / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D008099:Liver / Q000821:virology; D008217:Lymphocytic choriomeningitis virus; D051379:Mice