Hepatitis B Virus Transgenic Mice: Models of Viral Immunobiology and Pathogenesis

Abstract

The hepatitis B virus (HBV) is a noncytopathic, enveloped virus with a circular, double-stranded DNA genome that causes acute and chronic necroinflammatory liver disease and hepatocellular carcinoma (reviewed in CHISARI and FERRARI 1994). HBV infection acquired in adult life is often clinically inapparent and the vast majority of acutely infected adults recover completely from the disease and clear the virus. Rarely, however, the acute liver disease may be so severe that the patient can die from fulminant hepatitis. Approximately 5%–10% of acutely infected adults become persistently infected by the virus and develop chronic liver disease of varying severity. Neonatally transmitted HBV infection, however, is rarely cleared, and over 90% of such children become chronically infected. Because HBV is commonly spread from infected mother to newborn infant in highly populated areas of Africa and Asia, several hundred million people throughout the world are persistently infected by HBV for most of their lives and suffer varying degrees of chronic liver disease which greatly increases their risk of developing cirrhosis and hepatocellular carcinoma (HCC). Indeed, the risk of HCC is increased 100-fold in patients with chronic hepatitis, and the lifetime risk of HCC in males infected at birth approaches 40% (BEASLEY ET AL. 1981). Accordingly, a large fraction of the world’s population suffers and dies from these late complications of HBV infection.