Resistance to hepatitis C virus : potential genetic and immunological determinants
Studies of highly exposed individuals who remain seronegative (HESN) for HIV infection led to the discovery that homozygosity for the d32 mutation in the CCR5 chemokine receptor gene abrogated viral entry into target cells, and was associated with resistance to infection. In addition, evidence for protective immunity has been found in some HESN groups, such as sex workers in the Gambia. Population studies of those at high risk for hepatitis C virus (HCV) infection suggest that a HESN phenotype exists. There is a growing body of evidence for protective immunity, which allows clearance of HCV without seroconversion, and proof-of-principle evidence from in vitro studies that genetic polymorphisms may confer resistance to establishment of infection. This doctoral research project explores evidence for protective immunity, including via genetically programmed variations in host responses and provides evidence that genetic mutations confer resistance against HCV. The data generally strengthens the notion that investigations of naturally occurring polymorphisms within the HCV interactome, and genetic association studies of well-characterised HESN individuals, may identify potential targets for vaccine design and inform novel therapies.
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