Journal article
Evidence of viral adaptation to HLA class I-restricted immune pressure in chronic hepatitis C virus infection
Journal of Virology, Vol.80(22), pp.11094-11104
2006
Abstract
Cellular immune responses are an important correlate of hepatitis C virus (HCV) infection outcome. These responses are governed by the host's human leukocyte antigen (HLA) type, and HLA-restricted viral escape mutants are a critical aspect of this host-virus interaction. We examined the driving forces of HCV evolution by characterizing the in vivo selective pressure(s) exerted on single amino acid residues within nonstructural protein 3 (NS3) by the HLA types present in two host populations. Associations between polymorphisms within NS3 and HLA class I alleles were assessed in 118 individuals from Western Australia and Switzerland with chronic hepatitis C infection, of whom 82 (69%) were coinfected with human immunodeficiency virus. The levels and locations of amino acid polymorphisms exhibited within NS3 were remarkably similar between the two cohorts and revealed regions under functional constraint and selective pressures. We identified specific HCV mutations within and flanking published epitopes with the correct HLA restriction and predicted escaped amino acid. Additional HLA-restricted mutations were identified that mark putative epitopes targeted by cell-mediated immune responses. This analysis of host-virus interaction reveals evidence of HCV adaptation to HLA class I-restricted immune pressure and identifies in vivo targets of cellular immune responses at the population level.
Details
- Title
- Evidence of viral adaptation to HLA class I-restricted immune pressure in chronic hepatitis C virus infection
- Authors/Creators
- S. Gaudieri (Author/Creator) - Royal Perth HospitalA. Rauch (Author/Creator) - Royal Perth HospitalL.P. Park (Author/Creator) - Royal Perth HospitalE. Freitas (Author/Creator) - Royal Perth HospitalS. Herrmann (Author/Creator) - Royal Perth HospitalG. Jeffrey (Author/Creator) - Queen Elizabeth II Medical CentreW. Cheng (Author/Creator) - Royal Perth HospitalK. Pfafferott (Author/Creator) - Royal Perth HospitalK. Naidoo (Author/Creator) - Royal Perth HospitalR. Chapman (Author/Creator) - The University of Western AustraliaM. Battegay (Author/Creator) - University Hospital of BaselR. Weber (Author/Creator) - University Hospital of ZurichA. Telenti (Author/Creator) - University of LausanneH. Furrer (Author/Creator) - University Hospital of BernI. James (Author/Creator) - Royal Perth HospitalM. Lucas (Author/Creator) - Royal Perth HospitalS.A. Mallal (Author/Creator) - Royal Perth HospitalSwiss HIV Cohort Study (Author/Creator)
- Publication Details
- Journal of Virology, Vol.80(22), pp.11094-11104
- Publisher
- American Society for Microbiology
- Identifiers
- 991005542910007891
- Copyright
- © 2006, American Society for Microbiology
- Murdoch Affiliation
- Centre for Clinical Immunology and Biomedical Statistics
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.125 Hepatitis
- 1.125.83 HCV
- Web Of Science research areas
- Virology
- ESI research areas
- Microbiology