Einfluss von CD8 T-Zell-assoziiertem Selektionsdruck auf die Evolution des Hepatitis C Virus

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The hepatitis C virus (HCV) is a major cause of liver cirrhosis, liver failure and hepatocellular carcinoma, infecting an estimated 170 million individuals worldwide. The poor responsiveness to drug treatment, combined with limited access in the most critical regions of the world, has prompted efforts to develop an effective vaccine against HCV. Recent studies suggest that immune control of HCV is possible, specifically with cellular immune responses being essential for spontaneous resolution of acute HCV and protection from persistent infection in both humans and chimpanzees. The inherent sequence diversity of HCV represents one of the most substantial challenges to the development of an effective HCV vaccine. Not only does this pathogen continue to evolve in the host over the course of infection, but the global sequence diversity of HCV makes antigen selection for vaccines very difficult. In HIV and SIV, two other highly variable pathogens, numerous studies associate viral mutations with evasion of host antibody and CD8 T cell responses. The impact that this evolution can have on immune control can be profound. These studies are beginning to solidify our understanding of the role of host immune pressures in shaping the diversity of these pathogens. Therefore, understanding the relationship between HLA alleles, CD8 responses, and viral sequence diversity is necessary to elucidate the interaction between virus evolution and immune control of HCV, and help address the degree to which immune pressures are contributing to the global sequence diversity of HCV.