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Science. 2002 May 24;296(5572):1439-43.

Evidence of HIV-1 adaptation to HLA-restricted immune responses at a population level.

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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.


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.

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