Evidence of HIV-1 Adaptation to HLA-Restricted Immune Responses at a Population Level

C.B. Moore, M. John, I.R. James, Frank Christiansen, C.S. Witt, S.A. Mallal

    Research output: Contribution to journalArticle

    625 Citations (Scopus)

    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.
    Original languageEnglish
    Pages (from-to)1439-1443
    JournalScience
    Volume296
    Issue number24 May
    DOIs
    Publication statusPublished - 2002

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