WHY IMMUNE ESCAPE IS IMPORTANT

Knowledge of the molecular virology of the hepatitis viruses and the responses they elicit has emphasised the importance of host immunity in resolving infection and mediating liver damage. Many viruses cause cytolytic infections in which viral replication occurs at the expense of host cell viability. However this is a shortsighted strategy for the virus as it provides a clear “danger signal”1 that alerts the host’s innate and adaptive immune defences to eliminate the virus and terminate the infection. Such a life cycle requires a high rate of transmission from host to host, causes acute tissue damage and is unlikely to result in persistent infection. In order to cause chronic infection viruses must use strategies that enable them to evade or modify host immune responses sufficiently to prevent clearance. Of the hepatitis viruses only hepatitis B (HBV) and hepatitis C (HCV) viruses cause chronic infections and in order to do so they must evade host immune responses. Neither hepatitis A virus nor hepatitis E virus cause chronic infection and must be assumed to lack the ability to escape immune responses. Understanding the mechanisms used by HBV and HCV to evade host immunity is central to understanding their pathogenicity and necessary for the development of effective therapeutic strategies. Although knowledge of the mechanisms of immune escape by hepatitis viruses is increasing, considerable insight has come from the study of other viruses, some of which can cause hepatitis such as Epstein-Barr virus (EBV), HIV, and model systems such as murine lymphocytic choriomeningitis virus (LCMV), as well as transgenic mouse models of HBV infection. In both acute HBV and HCV infection a vigorous antiviral T lymphocyte response is associated with viral clearance. In chronic hepatitis B and hepatitis C virus specific T lymphocyte responses are weak or absent. The mechanisms leading to ineffectual …