Viral-host interactions in HBV Laboratory

Human hepatitis B virus (HBV) infection is a major worldwide health problem. Exposure to HBV can result in transient infection, with clearance of virus and immunity to reinfection, or chronic infection with carriage of the virus, often for the lifetime of the individual. These different outcomes are related to the dose of virus, age at the time of infection and the immune response generated towards viral antigens. Despite the availability of a HBV vaccine that protects against infection, no cures are available for chronic infection and many aspects of the disease are not understood.

Our laboratory studies the duck, woodchuck and chimpanzee models of human HBV infection using a range of in vivo (animal model), in vitro (cell culture), immunological (ELISA, immunostaining) and molecular techniques (PCR, RT PCR, southern blot and in situ hybridization).

The overall aims of our research are to understand why some individuals recover from HBV infection while others remain chronically infected. We have previously shown using Pekin ducks (Figure 1) that the outcome of Duck Hepatitis B Virus (DHBV) infection can be altered by age, dose of virus and antiviral drug treatment. We are extending this work to study the recovery phase of infection, to determine if removal of virus from the liver involves death of infected cells or if cells can be cured of infection by the action of cytokines, without cell death. We have recently determined that traces of viral DNA persist after recovery from infection and are investigating the form and activity of this viral DNA and its role in maintaining immunity to re-infection.

We are also developing therapies for treatment of chronic infections by combining antiviral drug therapy with various DNA vaccine protocols. DNA vaccine protocols include naked DNA vaccines, novel whole cell DNA vaccines and prime-boost protocols including DNA vaccine priming and boosting with recombinant fowlpox viruses.