{"id":315410,"date":"2016-11-03T13:02:40","date_gmt":"2016-11-03T20:02:40","guid":{"rendered":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/?post_type=msr-research-item&#038;p=315410"},"modified":"2018-10-16T20:06:46","modified_gmt":"2018-10-17T03:06:46","slug":"fine-mapping-classical-hla-variation-associated-durable-host-control-hiv-1-infection-african-americans","status":"publish","type":"msr-research-item","link":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/publication\/fine-mapping-classical-hla-variation-associated-durable-host-control-hiv-1-infection-african-americans\/","title":{"rendered":"Fine-mapping classical HLA variation associated with durable host control of HIV-1 infection in African Americans"},"content":{"rendered":"<p>A small proportion of human immunodeficiency virus-1 (HIV-1) infected individuals, termed HIV-1 controllers, suppress viral replication to very low levels in the absence of therapy. Genetic investigations of this phenotype have strongly implicated variation in the class I major histocompatibility complex (MHC) region as key to HIV-1 control. We collected sequence-based classical class I HLA genotypes at 4-digit resolution in HIV-1-infected African American controllers and progressors (<em>n<\/em> = 1107), and tested them for association with host control using genome-wide single nucleotide polymorphism data to account for population structure. Several classical alleles at <em>HLA-B<\/em> were associated with host control, including B*57:03 [odds ratio (OR) = 5.1; <em>P<\/em>= 3.4 \u00d7 10<sup>\u201318<\/sup>] and B*81:01 (OR = 4.8; <em>P<\/em>= 1.3 \u00d7 10<sup>\u22129<\/sup>). Analysis of variable amino acid positions demonstrates that HLA-B position 97 is the most significant association with host control in African Americans (omnibus <em>P<\/em> = 1.2 \u00d7 10<sup>\u221221<\/sup>) and explains the signal of several <em>HLA-B<\/em> alleles, including B*57:03. Within HLA-B, we also identified independent effects at position 116 (omnibus <em>P<\/em>= 2.8 \u00d7 10<sup>\u221215<\/sup>) in the canonical F pocket, position 63 in the B pocket (<em>P<\/em>= 1.5 \u00d7 10<sup>\u22123<\/sup>) and the non-pocket position 245 (<em>P<\/em>= 8.8 \u00d7 10<sup>\u221210<\/sup>), which is thought to influence CD8-binding kinetics. Adjusting for these HLA-B effects, there is evidence for residual association in the MHC region. These results underscore the key role of <em>HLA-B<\/em> in affecting HIV-1 replication, likely through the molecular interaction between HLA-B and viral peptides presented by infected cells, and suggest that sites outside the peptide-binding pocket also influence HIV-1 control.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>A small proportion of human immunodeficiency virus-1 (HIV-1) infected individuals, termed HIV-1 controllers, suppress viral replication to very low levels in the absence of therapy. Genetic investigations of this phenotype have strongly implicated variation in the class I major histocompatibility complex (MHC) region as key to HIV-1 control. We collected sequence-based classical class I HLA [&hellip;]<\/p>\n","protected":false},"featured_media":0,"template":"","meta":{"msr-url-field":"","msr-podcast-episode":"","msrModifiedDate":"","msrModifiedDateEnabled":false,"ep_exclude_from_search":false,"_classifai_error":"","msr-author-ordering":null,"msr_publishername":"","msr_publisher_other":"","msr_booktitle":"","msr_chapter":"","msr_edition":"","msr_editors":"","msr_how_published":"","msr_isbn":"","msr_issue":"19","msr_journal":"Human Molecular Genetics","msr_number":"","msr_organization":"","msr_pages_string":"4334-4347","msr_page_range_start":"4334","msr_page_range_end":"4347","msr_series":"","msr_volume":"21","msr_copyright":"","msr_conference_name":"","msr_doi":"10.1093\/hmg\/dds226","msr_arxiv_id":"","msr_s2_paper_id":"","msr_mag_id":"","msr_pubmed_id":"","msr_other_authors":"","msr_other_contributors":"","msr_speaker":"","msr_award":"","msr_affiliation":"","msr_institution":"","msr_host":"","msr_version":"","msr_duration":"","msr_original_fields_of_study":"","msr_release_tracker_id":"","msr_s2_match_type":"","msr_citation_count_updated":"","msr_published_date":"2012-06-19","msr_highlight_text":"","msr_notes":"","msr_longbiography":"","msr_publicationurl":"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/22718199","msr_external_url":"","msr_secondary_video_url":"","msr_conference_url":"","msr_journal_url":"","msr_s2_pdf_url":"","msr_year":0,"msr_citation_count":0,"msr_influential_citations":0,"msr_reference_count":0,"msr_s2_match_confidence":0,"msr_microsoftintellectualproperty":true,"msr_s2_open_access":false,"msr_s2_author_ids":[],"msr_pub_ids":[],"msr_hide_image_in_river":0,"footnotes":""},"msr-research-highlight":[],"research-area":[13553],"msr-publication-type":[193715],"msr-publisher":[],"msr-focus-area":[],"msr-locale":[268875],"msr-post-option":[],"msr-field-of-study":[],"msr-conference":[],"msr-journal":[],"msr-impact-theme":[],"msr-pillar":[],"class_list":["post-315410","msr-research-item","type-msr-research-item","status-publish","hentry","msr-research-area-medical-health-genomics","msr-locale-en_us"],"msr_publishername":"","msr_edition":"","msr_affiliation":"","msr_published_date":"2012-06-19","msr_host":"","msr_duration":"","msr_version":"","msr_speaker":"","msr_other_contributors":"","msr_booktitle":"","msr_pages_string":"4334-4347","msr_chapter":"","msr_isbn":"","msr_journal":"Human Molecular Genetics","msr_volume":"21","msr_number":"","msr_editors":"","msr_series":"","msr_issue":"19","msr_organization":"","msr_how_published":"","msr_notes":"","msr_highlight_text":"","msr_release_tracker_id":"","msr_original_fields_of_study":"","msr_download_urls":"","msr_external_url":"","msr_secondary_video_url":"","msr_longbiography":"","msr_microsoftintellectualproperty":1,"msr_main_download":"315425","msr_publicationurl":"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/22718199","msr_doi":"10.1093\/hmg\/dds226","msr_publication_uploader":[{"type":"file","title":"hum-mol-genet-2012-mclaren-4334-47","viewUrl":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-content\/uploads\/2016\/11\/Hum.-Mol.-Genet.-2012-McLaren-4334-47-2.pdf","id":315425,"label_id":0},{"type":"url","title":"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/22718199","viewUrl":false,"id":false,"label_id":0},{"type":"doi","title":"10.1093\/hmg\/dds226","viewUrl":false,"id":false,"label_id":0}],"msr_related_uploader":"","msr_citation_count":0,"msr_citation_count_updated":"","msr_s2_paper_id":"","msr_influential_citations":0,"msr_reference_count":0,"msr_arxiv_id":"","msr_s2_author_ids":[],"msr_s2_open_access":false,"msr_s2_pdf_url":null,"msr_attachments":[{"id":0,"url":"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/22718199"}],"msr-author-ordering":[{"type":"text","value":"Paul J. 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