The major genetic determinants of HIV-1 control affect HLA class I peptide presentation

The International HIV Controllers Study

Research output: Contribution to journalArticle

726 Scopus citations

Abstract

Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA-viral peptide interaction as the major factor modulating durable control of HIV infection.

Original languageEnglish (US)
Pages (from-to)1551-1557
Number of pages7
JournalScience
Volume330
Issue number6010
DOIs
StatePublished - Dec 10 2010

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ASJC Scopus subject areas

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