title: Evidence of HIV-1 adaptation to HLA-restricted immune responses at a population level.
abstract: Antigen-specific T cell immunity is HLA-restricted. Human immunodeficiency virus-type 1 (HIV-1) mutations that allow escape from host immune responses may therefore be HLA allele-specific. We analyzed HIV-1 reverse transcriptase sequences from a large HLA-diverse population of HIV-1-infected individuals. Polymorphisms in HIV-1 were most evident at sites of least functional or structural constraint and frequently were associated with particular host HLA class I alleles. Absence of polymorphism was also HLA allele-specific. At a population level, the degree of HLA-associated selection in viral sequence was predictive of viral load. These results support a fundamental role for HLA-restricted immune responses in driving and shaping HIV-1 evolution in vivo.
authors.affiliation: Centre for Clinical Immunology and Biomedical Statistics, Royal Perth Hospital and Murdoch University, Level 2 North Block, Royal Perth Hospital, Wellington Street, WA 6000, Australia.
authors.forename: Corey B
authors.initials: CB
authors.lastname: Moore
authors.forename: Mina
authors.initials: M
authors.lastname: John
authors.forename: Ian R
authors.initials: IR
authors.lastname: James
authors.forename: Frank T
authors.initials: FT
authors.lastname: Christiansen
authors.forename: Campbell S
authors.initials: CS
authors.lastname: Witt
authors.forename: Simon A
authors.initials: SA
authors.lastname: Mallal
mesh_terms: D000222:Adaptation, Physiological; D000483:Alleles; D015331:Cohort Studies; D016384:Consensus Sequence; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D005805:Genes, MHC Class I; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D006680:HLA Antigens / Q000235:genetics* / Q000276:immunology; D015234:HLA-A Antigens / Q000235:genetics / Q000276:immunology; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D016015:Logistic Models; D015999:Multivariate Analysis; D009154:Mutation; D011110:Polymorphism, Genetic; D012367:RNA, Viral / Q000097:blood; D012641:Selection, Genetic; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019562:Viral Load; D014904:Western Australia
chemical_list: D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D012367:RNA, Viral; D054303:HIV Reverse Transcriptase