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

TitleThe major genetic determinants of HIV-1 control affect HLA class I peptide presentation.
Publication TypeJournal Article
Year of Publication2010
AuthorsPereyra F, Jia X, McLaren PJ, et al.
Corporate AuthorsInternational HIV Controllers Study
JournalScience
Volume330
Issue6010
Pagination1551-7
Date Published2010 Dec 10
ISSN1095-9203
KeywordsAfrican Americans, Alleles, Amino Acids, Antigen Presentation, CD8-Positive T-Lymphocytes, Cohort Studies, Disease Progression, European Continental Ancestry Group, Genes, MHC Class I, Genome-Wide Association Study, Haplotypes, Hispanic Americans, HIV Antigens, HIV Infections, HIV Long-Term Survivors, HIV-1, HLA-A Antigens, HLA-B Antigens, HLA-C Antigens, Humans, Immunity, Innate, Logistic Models, Models, Molecular, Polymorphism, Single Nucleotide, Protein Conformation, Viral Load
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.

DOI10.1126/science.1195271
Alternate JournalScience
PubMed ID21051598
PubMed Central IDPMC3235490
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