{"id":321203,"date":"2016-11-14T12:42:05","date_gmt":"2016-11-14T20:42:05","guid":{"rendered":"https:\/\/www.microsoft.com\/en-us\/research\/?post_type=msr-research-item&#038;p=321203"},"modified":"2018-10-16T20:13:15","modified_gmt":"2018-10-17T03:13:15","slug":"increased-sequence-coverage-combined-targeting-variant-conserved-epitopes-correlates-control-hiv-replication","status":"publish","type":"msr-research-item","link":"https:\/\/www.microsoft.com\/en-us\/research\/publication\/increased-sequence-coverage-combined-targeting-variant-conserved-epitopes-correlates-control-hiv-replication\/","title":{"rendered":"Increased Sequence Coverage through Combined Targeting of Variant and Conserved Epitopes Correlates with Control of HIV Replication"},"content":{"rendered":"<p id=\"p-1\"><script src=\"https:\/\/apis.google.com\/_\/scs\/apps-static\/_\/js\/k=oz.gapi.en_US.YsRf0Y2ZnQE.O\/m=auth\/exm=plusone\/rt=j\/sv=1\/d=1\/ed=1\/am=AQ\/rs=AGLTcCNLi_p42du4_ThrE1DNk9nVaVls1Q\/cb=gapi.loaded_1\" async=\"\"><\/script><script src=\"https:\/\/apis.google.com\/_\/scs\/apps-static\/_\/js\/k=oz.gapi.en_US.YsRf0Y2ZnQE.O\/m=plusone\/rt=j\/sv=1\/d=1\/ed=1\/am=AQ\/rs=AGLTcCNLi_p42du4_ThrE1DNk9nVaVls1Q\/cb=gapi.loaded_0\" async=\"\"><\/script>A major challenge in the development of an HIV vaccine is that of contending with the extensive sequence variability found in circulating viruses. Induction of HIV-specific T-cell responses targeting conserved regions and induction of HIV-specific T-cell responses recognizing a high number of epitope variants have both been proposed as strategies to overcome this challenge. We addressed the ability of cytotoxic T lymphocytes from 30 untreated HIV-infected subjects with and without control of virus replication to recognize all clade B Gag sequence variants encoded by at least 5% of the sequences in the Los Alamos National Laboratory HIV database (1,300 peptides) using gamma interferon and interleukin-2 (IFN-\u03b3\/IL-2) FluoroSpot analysis. While targeting of conserved regions was similar in the two groups (<em>P<\/em> = 0.47), we found that subjects with control of virus replication demonstrated marginally lower recognition of Gag epitope variants than subjects with normal progression (<em>P<\/em> = 0.05). In viremic controllers and progressors, we found variant recognition to be associated with viral load (<em>r<\/em> = 0.62, <em>P<\/em> = 0.001). Interestingly, we show that increased overall sequence coverage, defined as the overall proportion of HIV database sequences targeted through the Gag-specific repertoire, is inversely associated with viral load (<em>r<\/em> = \u22120.38, <em>P<\/em> = 0.03). Furthermore, we found that sequence coverage, but not variant recognition, correlated with increased recognition of a panel of clade B HIV founder viruses (<em>r<\/em> = 0.50, <em>P<\/em> = 0.004). We propose sequence coverage by HIV Gag-specific immune responses as a possible correlate of protection that may contribute to control of virus replication. Additionally, sequence coverage serves as a valuable measure by which to evaluate the protective potential of future vaccination strategies.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>A major challenge in the development of an HIV vaccine is that of contending with the extensive sequence variability found in circulating viruses. Induction of HIV-specific T-cell responses targeting conserved regions and induction of HIV-specific T-cell responses recognizing a high number of epitope variants have both been proposed as strategies to overcome this challenge. We [&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":"2","msr_journal":"Journal of Virology","msr_number":"","msr_organization":"","msr_pages_string":"1354-1365","msr_page_range_start":"1354","msr_page_range_end":"1365","msr_series":"","msr_volume":"88","msr_copyright":"","msr_conference_name":"","msr_doi":"10.1128\/JVI.02361-13","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":"2013-08-19","msr_highlight_text":"","msr_notes":"","msr_longbiography":"","msr_publicationurl":"http:\/\/jvi.asm.org\/content\/88\/2\/1354.abstract","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-321203","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":"2013-08-19","msr_host":"","msr_duration":"","msr_version":"","msr_speaker":"","msr_other_contributors":"","msr_booktitle":"","msr_pages_string":"1354-1365","msr_chapter":"","msr_isbn":"","msr_journal":"Journal of Virology","msr_volume":"88","msr_number":"","msr_editors":"","msr_series":"","msr_issue":"2","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":"","msr_publicationurl":"http:\/\/jvi.asm.org\/content\/88\/2\/1354.abstract","msr_doi":"10.1128\/JVI.02361-13","msr_publication_uploader":[{"type":"url","title":"http:\/\/jvi.asm.org\/content\/88\/2\/1354.abstract","viewUrl":false,"id":false,"label_id":0},{"type":"doi","title":"10.1128\/JVI.02361-13","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":"http:\/\/jvi.asm.org\/content\/88\/2\/1354.abstract"}],"msr-author-ordering":[{"type":"text","value":"Justine Sunshine","user_id":0,"rest_url":false},{"type":"text","value":"Moon Kim","user_id":0,"rest_url":false},{"type":"user_nicename","value":"carlson","user_id":31333,"rest_url":"https:\/\/www.microsoft.com\/en-us\/research\/wp-json\/microsoft-research\/v1\/researchers?person=carlson"},{"type":"user_nicename","value":"heckerma","user_id":31991,"rest_url":"https:\/\/www.microsoft.com\/en-us\/research\/wp-json\/microsoft-research\/v1\/researchers?person=heckerma"},{"type":"text","value":"Julie Czartoski","user_id":0,"rest_url":false},{"type":"text","value":"Stephen A. 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