{"id":343673,"date":"2016-12-29T19:29:43","date_gmt":"2016-12-30T03:29:43","guid":{"rendered":"https:\/\/www.microsoft.com\/en-us\/research\/?post_type=msr-research-item&#038;p=343673"},"modified":"2018-10-16T21:43:19","modified_gmt":"2018-10-17T04:43:19","slug":"major-genetic-determinants-hiv-1-control-affect-hla-class-peptide-presentation-3","status":"publish","type":"msr-research-item","link":"https:\/\/www.microsoft.com\/en-us\/research\/publication\/major-genetic-determinants-hiv-1-control-affect-hla-class-peptide-presentation-3\/","title":{"rendered":"The Major Genetic Determinants of HIV-1 Control Affect HLA Class I Peptide Presentation"},"content":{"rendered":"<div id=\"content-block-markup\" data-highwire-cite-ref-tooltip-instance=\"highwire_reflinks_tooltip\" data-highwire-glossary-tooltip-instance=\"highwire_reflinks_tooltip\">\n<div class=\"article abstract-view\">\n<div id=\"abstract-3\" class=\"section abstract\">\n<p id=\"p-4\">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 <em>HLA-B<\/em> peptide binding groove, as well as an independent <em>HLA-C<\/em> effect, explain the SNP associations and reconcile both protective and risk <em>HLA<\/em> alleles. These results implicate the nature of the HLA\u2013viral peptide interaction as the major factor modulating durable control of HIV infection.<\/p>\n<\/div>\n<div id=\"fn-group-1\" class=\"section fn-group\"><\/div>\n<\/div>\n<p><span id=\"related-urls\"><\/span><\/div>\n","protected":false},"excerpt":{"rendered":"<p>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 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International HIV Controllers 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