The transgenic mouse model of hepatitis B virus infection

The hepatitis B virus (HBV) is a noncytopathic virus which causes a necroinflammatory liver disease of variable duration and severity. Studies of HBV pathogenesis have been difficult because of its limited host range (humans and chimpanzees) and by the lack of in vitro culture systems to propagate it. However, many questions relating to HBV biology, immunobiology and pathogenesis have been addressed in transgenic mouse models and will be discussed in this review. In particular the transgenic mouse model has been used to elucidate the pathogenetic potential of HBV and its products, the tissue specificity of viral gene expression and the intracellular trafficking of viral proteins. The pathogenetic role of the cytotoxic T lymphocyte (CTL) response to HBV has been demonstrated by the induction of a necroinflammatory liver disease following adoptive transfer of antigen specific CTL into HBV transgenic mice. Surprisingly, the antiviral potential of the CTL has been shown to be primarily mediated by noncytolytic mechanisms that involve the intrahepatic production of inflammatory cytokines. Elucidation of the immunological and virological basis for HBV persistence in the transgenic mouse model may yield immunotherapeutic and antiviral strategies to terminate chronic HBV infection. Finally, we will discuss the contribution of the transgenic mouse model to our understanding of the complex mechanisms responsible for the high incidence of hepatocellular carcinoma during chronic HBV infection.