Transgenic mice as a chemotherapeutic model for hepatitis B virus infection

Many transgenic mice carrying either portions of the hepatitis B virus (HBV) genome, or the complete genome, have been developed as models because HBV does not infect any other organisms besides humans and chimpanzees to cause a productive infection and disease. Some of these models have been useful in evaluating chemotherapeutic agents such as interferon-alpha, interleukins-2 and -12, other cytokines and nucleoside analogues for efficacy against HBV. A recently developed transgenic mouse (Guidotti et al., Journal of Virology 69:6158-6169.) which supports the replication of high levels of infectious HBV, provides the opportunity to evaluate the effect of antiviral drugs on various portions of the HBV life cycle in the whole animal. Evaluation of lamivudine, zidovudine and interferon-alpha B/D (IFN-alpha) in this HBV transgenic mouse model are described. Lamivudine and IFN-alpha were highly efficacious in reducing serum HBV DNA. As might be predicted, zidovudine was not efficacious. IFN-alpha was more effective in reducing virus titres in male mice as compared to female mice. This gender difference was not due to lower ability of female mice to express the virus. One anticipates that as this high level HBV transgenic-expressing mouse becomes more fully developed as a chemotherapeutic model, questions about the efficacy of different agents, routes of administration, synergy of antiviral combinations and novel drug therapies will be answered.