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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptation, Physiological
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Alleles
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Cohort Studies
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Consensus Sequence
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Epitopes, T-Lymphocyte / chemistry
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Epitopes, T-Lymphocyte / genetics
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Epitopes, T-Lymphocyte / immunology*
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Genes, MHC Class I
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HIV Infections / immunology*
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HIV Infections / virology
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HIV Reverse Transcriptase / chemistry
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HIV Reverse Transcriptase / genetics*
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HIV Reverse Transcriptase / immunology
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HIV-1 / genetics*
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HIV-1 / immunology
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HIV-1 / physiology
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HLA Antigens / genetics*
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HLA Antigens / immunology
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HLA-A Antigens / genetics
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HLA-A Antigens / immunology
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HLA-B Antigens / genetics
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HLA-B Antigens / immunology
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Humans
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Logistic Models
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Multivariate Analysis
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Mutation
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Polymorphism, Genetic*
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RNA, Viral / blood
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Selection, Genetic
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T-Lymphocytes, Cytotoxic / immunology*
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Viral Load
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Western Australia
Substances
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Epitopes, T-Lymphocyte
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HLA Antigens
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HLA-A Antigens
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HLA-B Antigens
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RNA, Viral
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HIV Reverse Transcriptase