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

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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.

Item Type:	Journal Article
Murdoch Affiliation(s):	Institute for Immunology and Infectious Diseases
Publisher:	American Association for the Advancement of Science
Copyright:	2010 by the American Association for the Advancement of Science
URI:	http://researchrepository.murdoch.edu.au/id/eprint/25816

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