Research Article

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

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Science  24 May 2002:
Vol. 296, Issue 5572, pp. 1439-1443
DOI: 10.1126/science.1069660

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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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