Grant: Master's Award - PA: RPP - Newfoundland and Labrador

Despite the availability of a vaccine, over 370 million people worldwide suffer from chronic hepatitis B virus (HBV) infection, over 600,000 persons die each year due to its consequences, and ~2 billion people show evidence of virus exposure. The virus does not directly cause liver injury but it is the immune reaction mounted against the infected liver cells that results in inflammation, known as hepatitis B. This inflammation can persist throughout life (chronic hepatitis) or may be clinically resolved. Either may lead to cirrhosis and liver cancer. It is difficult to study HBV in humans due to difficulties in identifying onset of infection and invasiveness of liver sample collection. Woodchuck hepatitis virus (WHV), a close relative of HBV, infecting the eastern North American woodchuck, is an excellent natural model of HBV infection and HBV-induced liver cancer. Most pathogens, including HBV, activate specific (adaptive) immune responses after the onset of infection. However, the mechanisms by which HBV is identified by the immune system are not understood. Recognition and early control of virus is a result of the nonspecific (innate) immune responses. The identification of Toll-like receptors (TLRs) and their role in innate immunity has been a recent focus of virology research. The overall goal of my research is to dissect which TLRs are involved in recognition of hepatitis virus and in activation of innate immune responses in the woodchuck model. This study will include recognition of how invading virus modulates activation of TLRs, particularly in liver and immune cells, which are both naturally targeted by HBV and WHV. The results may contribute to our better understanding not only how the immune system recognizes HBV immediately after invasion, but also could help in design of treatments altering TLR expression which may assist in early virus elimination and activation of a more effective immune response specifically directed against this virus.