Grant: Operating Grant

Hepatitis B virus (HBV) is an important human pathogen implicated in a wide range of clinical manifestations, ranging from cirrhosis, liver cancer and hepatic failure to seemingly asymptomatic and undetectable, by current clinical laboratory assays, occult HBV infection. Presently, an estimated 370 million people worldwide suffer from chronic liver diseases caused by HBV, 2 billion have been exposed to the virus and could be infected at low levels, and up to one million die annually because of HBV-induced liver pathology. In Canada, ~270,000 individuals have chonic hepatitis B. There is no effective treatment to completely eridicate the virus and, despite having vaccines, the number of people infected is not declining. The mechanisms governing establishment of persistent HBV infection, chronic hepatitis and virus-induced cancer remain under investigation, although meaningfull progress has been made in some areas. Since HBV infects only humans and higher primates and it cannot be studied simply in cell cultures, appropriate animal models are of primary importance. The woodchuck infected with woodchuck hepatitis virus (WHV) constitutes the most adequate system to study HBV infection and its pathological and epidemiological consequences. This rare experimental system is very well established in the applicant's laboratory. It has been successfully applied during the last two decades to recognize virological, molecular, cellular and immunological aspects of HBV infection, hepatitis B, HBV-induced liver cancer, and anti-HBV therapy. In the current studies, the model will be utilized to further advance knowledge by investigating yet unidentified elements of the natural history of infection, mechanisms of virus persistence, and roles of viral factors and host immune responses in the development and progression of liver disease and disorders of the immune system which seem to be associated with HBV infection.