Immunobiology and Pathogenesis of Hepatitis B and C Virus Infection
The outcome of noncytolytic viral infections is largely determined by the cellular immune response. Our laboratory focusses on the host-virus interactions that determine the outcome of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. Using a combination of real time viral dynamics and quantitative functional T cell analysis, we have demonstrated a direct relationship between viral clearance and the vigor, kinetics and homing potential of the antiviral T cell response to HBV and HCV, the rate with which they spread after inoculation and their ability to escape immune recognition. In addition, we have shown that there is a third effector limb in the immune response besides antibody neutralization and T cell-mediated destruction of infected cells: i.e. T cells also secrete antiviral cytokines that can purge viruses from infected cells without killing them. Currently we are applying genome-wide expression profiling to define the intracellular antiviral effector pathways that are triggered by these cytokines, and biochemical and molecular approaches to identify the points in the life cycles of these viruses that are interrupted by their antiviral effects.