title: Resistance to hepatitis C virus: potential genetic and immunological determinants.
abstract: Studies of individuals who were highly exposed but seronegative (HESN) for HIV infection led to the discovery that homozygosity for the Δ32 deletion mutation in the CCR5 gene prevents viral entry into target cells, and is associated with resistance to infection. Additionally, evidence for protective immunity has been noted in some HESN groups, such as sex workers in The Gambia. Population studies of individuals at high risk for hepatitis C virus infection suggest that an HESN phenotype exists. The body of evidence, which suggests that protective immunity allows clearance of hepatitis C virus without seroconversion is growing. Furthermore, proof-of-principle evidence from in-vitro studies shows that genetic polymorphisms can confer resistance to establishment of infection. This Review discusses the possibility that genetic mutations confer resistance against hepatitis C virus, and also explores evidence for protective immunity, including via genetically programmed variations in host responses. The data generally strengthens the notion that investigations of naturally arising polymorphisms within the hepatitis C virus interactome, and genetic association studies of well characterised HESN individuals, could identify potential targets for vaccine design and inform novel therapies.
authors.affiliation: Inflammation and Infection Research Centre, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia. Electronic address: m.mina@student.unsw.edu.au.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Mina
authors.affiliation: Inflammation and Infection Research Centre, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Fabio
authors.initials: F
authors.lastname: Luciani
authors.affiliation: Inflammation and Infection Research Centre, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Barbara
authors.initials: B
authors.lastname: Cameron
authors.affiliation: Inflammation and Infection Research Centre, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Rowena A
authors.initials: RA
authors.lastname: Bull
authors.affiliation: School of Molecular and Biomedical Science, University of Adelaide, Adelaide, SA, Australia; Centre for Cancer Biology, SA Pathology, Adelaide, SA, Australia.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Beard
authors.affiliation: Westmead Millennium Institute, University of Sydney, Sydney, NSW, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Booth
authors.affiliation: Inflammation and Infection Research Centre, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Lloyd
mesh_terms: D060467:Disease Resistance; D056726:Genetic Association Studies; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000235:genetics* / Q000276:immunology*; D054884:Host-Pathogen Interactions; D006801:Humans; D011110:Polymorphism, Genetic