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Summary Hepatitis C virus (HCV) infects more than 180 million of the world’s population and causes a persistent infection that over decades can result in cirrhosis and hepatocellular carcinoma. Treatment is only partially effective and control is likely only with the development of effective vaccines. Currently, only chimpanzees can be infected with HCV and alternative animal and tissue culture models are badly needed. We have used mice transgenic for HLA-DR and human CD4 to analyse the specificity of murine responses to the HCV NS3 antigen in an effort to determine whether the epitopes recognized correspond to those recognized by human T cells. Indeed, determinants mapped in transgenic mice overlap with those in a patient exposed to HCV through infection. This result provides hope that such an animal model may be a useful tool with which to analyse particular aspects of immune responses to HCV in vivo . [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) is yet another example of a pathogen that persists in the presence of a readily apparent immune response. A evidence for both humoral and cellular immune responsiveness is quite strong, our studies have begun to examine whether qualitative defects in CD4 T-cell responses to viral antigens may help to explain why HCV is not eliminated in the vast majority of infections. Direct evidence that CD4 T cells play a role in HCV persistence is lacking, but several observations are consistent with this possibility. Importantly, it does not exclude the role of antibody or killer T cells in the immunopathogenesis of HCV infection. In addition, we discuss the consequences of viral mutation and how naturally occurring variants in immunodominant viral epitopes can effectively suppress helper T-cell responses to wild type virus. [ABSTRACT FROM AUTHOR]