LIVER IVM AND HBV · Imaging liver immunopathology by intravital microscopy (IVM): a new approach to study the pathogenesis of hepatitis B virus (HBV) infection

Overall objective and Specific Aims. The overall objective of this proposal is to elucidate the pathogenesis ofHBV infection with the ultimate hope that this knowledge will lead to the development of new therapeuticstrategies to terminate persistent infection and its attendant costs and complications. Our approach is to dissectpoorly understood cellular and molecular pathways responsible for both liver disease and viral clearance takingadvantage of technological advances in the field of live imaging and unique mouse models of HBV infection.Three specific aims will be pursued:1. Visualize and characterize where and how naïve and effector CTL of different specificities adhere tovessels and recognize/kill HBV-expressing hepatocytes within the “normal”, fibrotic/cirrhotic orcancerous liver.2. Characterize the role of platelets in HBV pathogenesis.3. Characterize the role of Kupffer cells in HBV pathogenesis.