Young S. Hahn, PhD
Molecular mechanisms of immune modulation by Hepatitis C virus; immunopathogenesis of liver damage
Hepatitis C virus (HCV) infection in humans is almost invariably associated with viral persistence. HCV persistent infection is a major risk factor for the development of hepatocellular carcinoma and also leads to the development of autoimmune disease. The high incidence of persistent infection with HCV suggests that this virus has evolved one or more mechanisms to evade and possibly suppress the host immune response. To dissect the molecular mechanism of immune modulation by HCV core and immunopathogenesis of liver damage, the Hahn lab has developed a murine model of HCV core transgenic mice by directing the expression of HCV core protein in hepatocytes.
Hahn and others demonstrated that HCV core is associated with the cytoplasmic domain of Fas, a member of TNFR family. Intriguingly, this interaction increases the susceptibility of hepatocytes to Fas-mediated apoptosis. Strikingly, similar to chronic hepatitis C in human, massive lymphocytic infiltration was notable around the portal tract of liver in core transgenic mice and these intrahepatic lymphocytes were associated with liver damage. Importantly, the sustained liver inflammation led to the development of liver cirrhosis. These results suggest that liver-infiltrating lymphocytes induced by core protein may play a pivotal role in liver damage.
Using HCV core transgenic system, they are investigating the role of HCV core on immune modulation and its consequence on the development of liver damage. Currently, they are analyzing the regulation of hepatocyte inflammatory activation by liver-infiltrating lymphocytes. In addition, they are exploring the molecular mechanism of hepatocyte damage by liver-infiltrating lymphocytes in HCV core transgenic mice in collaboration with Dr. Ulike Lorenz who has an expertise on studying the intracellular signaling event of T cell activation.