Evidence of HIV-1 Adaptation to HLA-Restricted Immune Responses at a Population Level
Moore, C.B., John, M., James, I.R., Christiansen, F.T., Witt, C.S. and Mallal, S. (2002) Evidence of HIV-1 Adaptation to HLA-Restricted Immune Responses at a Population Level. Science, 296 (5572). pp. 1439-1443.
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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.
|Publication Type:||Journal Article|
|Murdoch Affiliation:||Centre for Clinical Immunology and Biomedical Statistics|
|Publisher:||American Association for the Advancement of Science|
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