{"id":157461,"date":"2008-01-01T00:00:00","date_gmt":"2008-01-01T00:00:00","guid":{"rendered":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/msr-research-item\/human-leukocyte-antigen-specific-polymorphisms-in-hiv-1-gag-and-their-association-with-viral-load-in-chronic-untreated-infection\/"},"modified":"2018-10-16T22:11:54","modified_gmt":"2018-10-17T05:11:54","slug":"human-leukocyte-antigen-specific-polymorphisms-in-hiv-1-gag-and-their-association-with-viral-load-in-chronic-untreated-infection","status":"publish","type":"msr-research-item","link":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/publication\/human-leukocyte-antigen-specific-polymorphisms-in-hiv-1-gag-and-their-association-with-viral-load-in-chronic-untreated-infection\/","title":{"rendered":"Human leukocyte antigen-specific polymorphisms in HIV-1 Gag and their association with viral load in chronic untreated infection"},"content":{"rendered":"
\n

Objective: Selection of specific human leukocyte antigen (HLA)-restricted cytotoxic T-lymphocyte (CTL) escape mutations in key Gag epitopes has been associated with loss of HIV immune control on an individual basis. Here we undertake a population-based identification of HLA-associated polymorphisms in Gag and investigate their relationship with plasma viral load.<\/p>\n

Design: Cross-sectional analysis of 567 chronically HIV subtype B-infected, treatment-naive individuals.<\/p>\n

Methods: HLA class I-associated Gag substitutions were identified using phylogenetically corrected analysis methods featuring a multivariate adjustment for HLA linkage disequilibrium and a q<\/em>-value correction for multiple tests. Presence of HLA-associated substitutions and markers of HIV disease status were correlated using Spearman’s rank test.<\/p>\n

Results: We have created a gene-wide map of HLA class I-associated substitutions in HIV-1 subtype B Gag. This features 111 HLA-associated substitutions occurring at 51 of 500 Gag codons, more than 50% of which occur within published and\/or putative HLA-restricted CTL epitopes. A modest inverse correlation was observed between the total number of HLA-associated Gag polymorphic sites within each individual and plasma viral load in chronic untreated infection (R<\/em> = \u22120.17, P<\/em> < 0.0001), supporting the hypothesis that a broad ability to target Gag in vivo<\/em> contributes to viral control. A modest positive correlation was observed between the proportion of these sites exhibiting HLA-associated substitutions and plasma viral load (R<\/em> = 0.09, P<\/em> = 0.03), consistent with a loss of viremia control with the accumulation of CTL escape mutations.<\/p>\n

Conclusion: Results contribute to our understanding of immune-driven viral adaptation and suggest that the accumulation of CTL escape mutations in Gag results in clinically detectable consequences at the population level. These data have implications for HIV vaccines.<\/p>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

Objective: Selection of specific human leukocyte antigen (HLA)-restricted cytotoxic T-lymphocyte (CTL) escape mutations in key Gag epitopes has been associated with loss of HIV immune control on an individual basis. Here we undertake a population-based identification of HLA-associated polymorphisms in Gag and investigate their relationship with plasma viral load. Design: Cross-sectional analysis of 567 chronically […]<\/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":"AIDS","msr_editors":"","msr_how_published":"","msr_isbn":"","msr_issue":"","msr_journal":"","msr_number":"11","msr_organization":"","msr_pages_string":"1277\u20131286","msr_page_range_start":"1277","msr_page_range_end":"1286","msr_series":"","msr_volume":"22","msr_copyright":"","msr_conference_name":"AIDS","msr_doi":"10.1097\/QAD.0b013e3283021a8c","msr_arxiv_id":"","msr_s2_paper_id":"","msr_mag_id":"","msr_pubmed_id":"","msr_other_authors":"Zabrina L Brumme, Iris Tao, Sharon Szeto, Chanson J Brumme, Christian Brander, Bruce Walker, P Richard Harrigan, Dennison Chan, Nicole Frahm","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":"2008-01-01","msr_highlight_text":"","msr_notes":"","msr_longbiography":"","msr_publicationurl":"","msr_external_url":"","msr_secondary_video_url":"","msr_conference_url":"","msr_journal_url":"","msr_s2_pdf_url":"","msr_year":2008,"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":[193716],"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-157461","msr-research-item","type-msr-research-item","status-publish","hentry","msr-research-area-medical-health-genomics","msr-locale-en_us"],"msr_publishername":"","msr_edition":"AIDS","msr_affiliation":"","msr_published_date":"2008-01-01","msr_host":"","msr_duration":"","msr_version":"","msr_speaker":"","msr_other_contributors":"","msr_booktitle":"","msr_pages_string":"1277\u20131286","msr_chapter":"","msr_isbn":"","msr_journal":"","msr_volume":"22","msr_number":"11","msr_editors":"","msr_series":"","msr_issue":"","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":"457272","msr_publicationurl":"","msr_doi":"10.1097\/QAD.0b013e3283021a8c","msr_publication_uploader":[{"type":"file","title":"Human leukocyte antigen-specific polymorphisms in HIV-1 Gag and their association with viral load in chronic untreated infection","viewUrl":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-content\/uploads\/2008\/01\/Human_leukocyte_antigen_specific_polymorphisms_in.4.pdf","id":457272,"label_id":0},{"type":"doi","title":"10.1097\/QAD.0b013e3283021a8c","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":[],"msr-author-ordering":[{"type":"text","value":"Zabrina L Brumme","user_id":0,"rest_url":false},{"type":"text","value":"Iris Tao","user_id":0,"rest_url":false},{"type":"text","value":"Sharon Szeto","user_id":0,"rest_url":false},{"type":"text","value":"Chanson J Brumme","user_id":0,"rest_url":false},{"type":"user_nicename","value":"carlson","user_id":31333,"rest_url":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/microsoft-research\/v1\/researchers?person=carlson"},{"type":"text","value":"Dennison Chan","user_id":0,"rest_url":false},{"type":"user_nicename","value":"carlk","user_id":31331,"rest_url":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/microsoft-research\/v1\/researchers?person=carlk"},{"type":"text","value":"Nicole Frahm","user_id":0,"rest_url":false},{"type":"text","value":"Christian Brander","user_id":0,"rest_url":false},{"type":"text","value":"Bruce Walker","user_id":0,"rest_url":false},{"type":"user_nicename","value":"heckerma","user_id":31991,"rest_url":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/microsoft-research\/v1\/researchers?person=heckerma"},{"type":"text","value":"P. 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