Grant: Project Grant

The hepatitis B virus (HBV) is a major cause of severe liver disease worldwide, including cirrhosis and liver cancer. There are drugs that can control the virus but they do not cure chronic infection. There is a need for greater understanding of the immune response after exposure to virus and in the early acute infection and during long-term chronic infection in order to develop better therapies. Some subspecies of woodchucks (i.e., groundhogs) can be infected with woodchuck hepatitis virus (WHV) a cousin of the HBV, and also develop hepatitis (liver inflammation) and associated liver cancer similar to people. WHV infection in woodchucks is a valuable model helping to understand how liver disease and cancer develops. This animal model is also important for testing of new antiviral drugs. Until now, most assessments of the immune response to HBV infection and to treatment were done by evaluating surrogate markers in blood. We will use well-established conventional tests along with advanced live cell imaging within the liver to assess in real time the immune response to early and long-term WHV infection and after treatment with an antiviral drugs. Our team are experts in liver disease, virology, HBV pathogenesis, in the woodchuck HBV model, woodchuck husbandry, and in using live cell imaging. We will assess, for the first time, virus-cell and cell-cell interactions inside the living liver in response to virus infection, in different stages of liver disease and during anti-viral treatment. This study will ultimately contribute to the development of new treatments aiming to achieve a cure for chronic hepatitis B and complete protection against liver cancer caused by the HBV.