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

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Publication date 2010
Author International HIV Controllers Study, Pereyra Florencia, Jia Xiaoming, McLaren Paul J, Telenti Amalio, de Bakker Paul I W, Walker Bruce D, Ripke Stephan, Brumme Chanson J, Pulit Sara L, Carrington Mary, Kadie Carl M, Carlson Jonathan M, Heckerman David, Graham Robert R, Plenge Robert M, Deeks Steven G, Gianniny Lauren, Crawford Gabriel, Sullivan Jordan, Gonzalez Elena, Davies Leela, Camargo Amy, Moore Jamie M, Beattie Nicole,
Project Host evolutionary genomics of HIV-1 and other retroviruses
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Original article (peer-reviewed)

Journal Science (New York, N.Y.)
Volume (Issue) 330(6010)
Page(s) 1551 - 7
Title of proceedings Science (New York, N.Y.)
DOI 10.1126/science.1195271

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.
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