HLA class I-mediated selection of immune escape mutations in functionally important Gag epitopes may partly explain slower disease progression in HIV-1-infected individuals with protective HLA alleles. To investigate the impact of Gag function on disease progression, the replication capacities of viruses encoding Gag-protease from 60 individuals in early HIV-1 subtype C infection were assayed in an HIV-1-inducible green fluorescent protein reporter cell line and were correlated with subsequent disease progression. Replication capacities did not correlate with viral load set points (p=0.37) but were significantly lower in individuals with below median viral load set points (p=0.03), and there was a trend of correlation between lower replication capacities and slower rates of CD4 decline (p=0.09). Overall, the proportion of host HLA-specific Gag polymorphisms in or adjacent to epitopes was negatively associated with replication capacities (p=0.04) but host HLA-B-specific polymorphisms were associated with higher viral load set points (p=0.01). Further, polymorphisms associated with host-specific protective HLA alleles were linked with higher viral load set points (p=0.03). These data suggest that transmission or early HLA-driven selection of Gag polymorphisms results in reduced early cytotoxic T-lymphocyte (CTL) responses and higher viral load set points. In support of the former, 46 percent of individuals with non-protective alleles harboured a Gag polymorphism exclusively associated with a protective HLA allele, indicating a high rate of their transmission in sub-Saharan Africa. Overall, HIV disease progression is likely to be affected by the ability to mount effective Gag CTL responses as well as the replication capacity of the transmitted virus.<\/p>\n","protected":false},"excerpt":{"rendered":"
HLA class I-mediated selection of immune escape mutations in functionally important Gag epitopes may partly explain slower disease progression in HIV-1-infected individuals with protective HLA alleles. To investigate the impact of Gag function on disease progression, the replication capacities of viruses encoding Gag-protease from 60 individuals in early HIV-1 subtype C infection were assayed in […]<\/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":"","msr_journal":"","msr_number":"","msr_organization":"","msr_pages_string":"","msr_page_range_start":"","msr_page_range_end":"","msr_series":"","msr_volume":"","msr_copyright":"","msr_conference_name":"","msr_doi":"10.1128\/JVI.02520-10","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":"2011-02-02","msr_highlight_text":"","msr_notes":"","msr_longbiography":"","msr_publicationurl":"http:\/\/jvi.asm.org\/content\/early\/2011\/02\/02\/JVI.02520-10.short","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-322784","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":"2011-02-02","msr_host":"","msr_duration":"","msr_version":"","msr_speaker":"","msr_other_contributors":"","msr_booktitle":"","msr_pages_string":"","msr_chapter":"","msr_isbn":"","msr_journal":"","msr_volume":"","msr_number":"","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":"","msr_publicationurl":"http:\/\/jvi.asm.org\/content\/early\/2011\/02\/02\/JVI.02520-10.short","msr_doi":"10.1128\/JVI.02520-10","msr_publication_uploader":[{"type":"url","title":"http:\/\/jvi.asm.org\/content\/early\/2011\/02\/02\/JVI.02520-10.short","viewUrl":false,"id":false,"label_id":0},{"type":"doi","title":"10.1128\/JVI.02520-10","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\/early\/2011\/02\/02\/JVI.02520-10.short"}],"msr-author-ordering":[{"type":"text","value":"Jaclyn K. Wright","user_id":0,"rest_url":false},{"type":"text","value":"Vladimir Novitsky","user_id":0,"rest_url":false},{"type":"text","value":"Mark A. Brockman","user_id":0,"rest_url":false},{"type":"text","value":"Zabrina L. Brumme","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":"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":"Bingxia Wang","user_id":0,"rest_url":false},{"type":"text","value":"Elena Losina","user_id":0,"rest_url":false},{"type":"text","value":"Mopo Leshwedi","user_id":0,"rest_url":false},{"type":"text","value":"Mary van der Stok","user_id":0,"rest_url":false},{"type":"text","value":"Lungile Maphumulo","user_id":0,"rest_url":false},{"type":"text","value":"Nompumelelo Mkhwanazi","user_id":0,"rest_url":false},{"type":"text","value":"Fundisiwe Chonco","user_id":0,"rest_url":false},{"type":"text","value":"Philip J. R. Goulder","user_id":0,"rest_url":false},{"type":"text","value":"Max Essex","user_id":0,"rest_url":false},{"type":"text","value":"Bruce D. Walker","user_id":0,"rest_url":false},{"type":"text","value":"Thumbi Ndung'u","user_id":0,"rest_url":false}],"msr_impact_theme":[],"msr_research_lab":[],"msr_event":[],"msr_group":[],"msr_project":[],"publication":[],"video":[],"msr-tool":[],"msr_publication_type":"article","related_content":[],"_links":{"self":[{"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-research-item\/322784","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-research-item"}],"about":[{"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/types\/msr-research-item"}],"version-history":[{"count":1,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-research-item\/322784\/revisions"}],"predecessor-version":[{"id":524875,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-research-item\/322784\/revisions\/524875"}],"wp:attachment":[{"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/media?parent=322784"}],"wp:term":[{"taxonomy":"msr-research-highlight","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-research-highlight?post=322784"},{"taxonomy":"msr-research-area","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/research-area?post=322784"},{"taxonomy":"msr-publication-type","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-publication-type?post=322784"},{"taxonomy":"msr-publisher","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-publisher?post=322784"},{"taxonomy":"msr-focus-area","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-focus-area?post=322784"},{"taxonomy":"msr-locale","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-locale?post=322784"},{"taxonomy":"msr-post-option","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-post-option?post=322784"},{"taxonomy":"msr-field-of-study","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-field-of-study?post=322784"},{"taxonomy":"msr-conference","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-conference?post=322784"},{"taxonomy":"msr-journal","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-journal?post=322784"},{"taxonomy":"msr-impact-theme","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-impact-theme?post=322784"},{"taxonomy":"msr-pillar","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-pillar?post=322784"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}