{"id":322730,"date":"2016-11-16T08:01:30","date_gmt":"2016-11-16T16:01:30","guid":{"rendered":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/?post_type=msr-research-item&#038;p=322730"},"modified":"2018-10-16T20:15:56","modified_gmt":"2018-10-17T03:15:56","slug":"hla-associated-alterations-replication-capacity-chimeric-nl4-3-viruses-carrying-gag-protease-elite-controllers-human-immunodeficiency-virus-type-1","status":"publish","type":"msr-research-item","link":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/publication\/hla-associated-alterations-replication-capacity-chimeric-nl4-3-viruses-carrying-gag-protease-elite-controllers-human-immunodeficiency-virus-type-1\/","title":{"rendered":"HLA-Associated Alterations in Replication Capacity of Chimeric NL4-3 Viruses Carrying gag-protease from Elite Controllers of Human Immunodeficiency Virus Type 1"},"content":{"rendered":"<p id=\"p-1\"><script src=\"https:\/\/apis.google.com\/_\/scs\/apps-static\/_\/js\/k=oz.gapi.en_US.yyEW3a5n8RU.O\/m=auth\/exm=plusone\/rt=j\/sv=1\/d=1\/ed=1\/am=AQ\/rs=AGLTcCNKDGLj8ycC1htqFS9xJtcAdG-Ffg\/cb=gapi.loaded_1\" async=\"\"><\/script><script src=\"https:\/\/apis.google.com\/_\/scs\/apps-static\/_\/js\/k=oz.gapi.en_US.yyEW3a5n8RU.O\/m=plusone\/rt=j\/sv=1\/d=1\/ed=1\/am=AQ\/rs=AGLTcCNKDGLj8ycC1htqFS9xJtcAdG-Ffg\/cb=gapi.loaded_0\" async=\"\"><\/script>Human immunodeficiency virus type 1 (HIV-1)-infected persons who maintain plasma viral loads of <50 copies RNA\/ml without treatment have been termed elite controllers (EC). Factors contributing to durable control of HIV in EC are unknown, but an HLA-dependent mechanism is suggested by overrepresentation of \u201cprotective\u201d class I alleles, such as B*27, B*51, and B*57. Here we investigated the relative replication capacity of viruses (VRC) obtained from EC (<em>n<\/em> = 54) compared to those from chronic progressors (CP; <em>n<\/em> = 41) by constructing chimeric viruses using patient-derived <em>gag-protease<\/em> sequences amplified from plasma HIV RNA and inserted into an NL4-3 backbone. The chimeric viruses generated from EC displayed lower VRC than did viruses from CP (<em>P<\/em> < 0.0001). HLA-B*57 was associated with lower VRC (<em>P<\/em> = 0.0002) than were other alleles in both EC and CP groups. Chimeric viruses from B*57<sup>+<\/sup> EC (<em>n<\/em> = 18) demonstrated lower VRC than did viruses from B*57<sup>+<\/sup> CP (<em>n<\/em> = 8, <em>P<\/em> = 0.0245). Differences in VRC between EC and CP were also observed for viruses obtained from individuals expressing no described \u201cprotective\u201d alleles (<em>P<\/em> = 0.0065). Intriguingly, two common HLA alleles, A*02 and B*07, were associated with higher VRC (<em>P<\/em> = 0.0140 and 0.0097, respectively), and there was no difference in VRC between EC and CP sharing these common HLA alleles. These findings indicate that cytotoxic T-lymphocyte (CTL) selection pressure on <em>gag-protease<\/em> alters VRC, and HIV-specific CTLs inducing escape mutations with fitness costs in this region may be important for strict viremia control in EC of HIV.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Human immunodeficiency virus type 1 (HIV-1)-infected persons who maintain plasma viral loads of<\/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":"1","msr_journal":"Journal of Virology","msr_number":"","msr_organization":"","msr_pages_string":"140-149","msr_page_range_start":"140","msr_page_range_end":"149","msr_series":"","msr_volume":"83","msr_copyright":"","msr_conference_name":"","msr_doi":"10.1128\/JVI.01471-08","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":"2009-01-05","msr_highlight_text":"","msr_notes":"","msr_longbiography":"","msr_publicationurl":"http:\/\/jvi.asm.org\/content\/83\/1\/140.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-322730","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":"2009-01-05","msr_host":"","msr_duration":"","msr_version":"","msr_speaker":"","msr_other_contributors":"","msr_booktitle":"","msr_pages_string":"140-149","msr_chapter":"","msr_isbn":"","msr_journal":"Journal of Virology","msr_volume":"83","msr_number":"","msr_editors":"","msr_series":"","msr_issue":"1","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\/83\/1\/140.abstract","msr_doi":"10.1128\/JVI.01471-08","msr_publication_uploader":[{"type":"url","title":"http:\/\/jvi.asm.org\/content\/83\/1\/140.abstract","viewUrl":false,"id":false,"label_id":0},{"type":"doi","title":"10.1128\/JVI.01471-08","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\/83\/1\/140.abstract"}],"msr-author-ordering":[{"type":"text","value":"Toshiyuki Miura","user_id":0,"rest_url":false},{"type":"text","value":"Mark A. 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