{"id":157460,"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\/marked-epitope-and-allele-specific-differences-in-rates-of-mutation-in-human-immunodeficiency-type-1-hiv-1-gag-pol-and-nef-cytotoxic-t-lymphocyte-epitopes-in-acuteearly-hiv-1-infection\/"},"modified":"2018-10-16T22:21:56","modified_gmt":"2018-10-17T05:21:56","slug":"marked-epitope-and-allele-specific-differences-in-rates-of-mutation-in-human-immunodeficiency-type-1-hiv-1-gag-pol-and-nef-cytotoxic-t-lymphocyte-epitopes-in-acuteearly-hiv-1-infection","status":"publish","type":"msr-research-item","link":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/publication\/marked-epitope-and-allele-specific-differences-in-rates-of-mutation-in-human-immunodeficiency-type-1-hiv-1-gag-pol-and-nef-cytotoxic-t-lymphocyte-epitopes-in-acuteearly-hiv-1-infection\/","title":{"rendered":"Marked Epitope- and Allele-Specific Differences in Rates of Mutation in Human Immunodeficiency Type 1 (HIV-1) Gag, Pol, and Nef Cytotoxic T-Lymphocyte Epitopes in Acute\/Early HIV-1 Infection"},"content":{"rendered":"<div class=\"asset-content\">\n<p>During acute human immunodeficiency virus type 1 (HIV-1) infection, early host cellular immune responses drive viral evolution. The rates and extent of these mutations, however, remain incompletely characterized. In a cohort of 98 individuals newly infected with HIV-1 subtype B, we longitudinally characterized the rates and extent of HLA-mediated escape and reversion in Gag, Pol, and Nef using a rational definition of HLA-attributable mutation based on the analysis of a large independent subtype B data set. We demonstrate rapid and dramatic HIV evolution in response to immune pressures that in general reflect established cytotoxic T-lymphocyte (CTL) response hierarchies in early infection. On a population level, HLA-driven evolution was observed in [ ]80% of published CTL epitopes. Five of the 10 most rapidly evolving epitopes were restricted by protective HLA alleles (HLA-B*13\/B*51\/B*57\/B*5801; P=0.01), supporting the importance of a strong early CTL response in HIV control. Consistent with known fitness costs of escape, B*57-associated mutations in Gag were among the most rapidly reverting positions upon transmission to non-B*57-expressing individuals, whereas many other HLA-associated polymorphisms displayed slow or negligible reversion. Overall, an estimated minimum of 30% of observed substitutions in Gag\/Pol and 60% in Nef were attributable to HLA-associated escape and reversion events. Results underscore the dominant role of immune pressures in driving early within-host HIV evolution. Dramatic differences in escape and reversion rates across codons, genes, and HLA restrictions are observed, highlighting the complexity of viral adaptation to the host immune response.<\/p>\n<\/div>\n<p><!-- .asset-content --><\/p>\n","protected":false},"excerpt":{"rendered":"<p>During acute human immunodeficiency virus type 1 (HIV-1) infection, early host cellular immune responses drive viral evolution. The rates and extent of these mutations, however, remain incompletely characterized. In a cohort of 98 individuals newly infected with HIV-1 subtype B, we longitudinally characterized the rates and extent of HLA-mediated escape and reversion in Gag, Pol, [&hellip;]<\/p>\n","protected":false},"featured_media":230089,"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":"Journal of Virology","msr_editors":"","msr_how_published":"","msr_isbn":"","msr_issue":"","msr_journal":"Journal of Virology","msr_number":"","msr_organization":"","msr_pages_string":"9216-9227","msr_page_range_start":"9216","msr_page_range_end":"9227","msr_series":"","msr_volume":"82","msr_copyright":"","msr_conference_name":"","msr_doi":"","msr_arxiv_id":"","msr_s2_paper_id":"","msr_mag_id":"","msr_pubmed_id":"","msr_other_authors":"Zabrina L. Brumme, Chanson J. Brumme, Hendrik Streeck, Mina John, Quentin Eichbaum, Brian L. Block, Brett Baker, Martin Markowitz, Heiko Jessen, Anthony D. Kelleher, Eric Rosenberg, John Kaldor, Yuko Yuki, Mary Carrington, Todd M. Allen, Simon Mallal, Marcus Altfeld, Bruce D. Walker","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":"http:\/\/jvi.asm.org\/cgi\/content\/abstract\/82\/18\/9216","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":[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-157460","msr-research-item","type-msr-research-item","status-publish","has-post-thumbnail","hentry","msr-research-area-medical-health-genomics","msr-locale-en_us"],"msr_publishername":"","msr_edition":"Journal of Virology","msr_affiliation":"","msr_published_date":"2008-01-01","msr_host":"","msr_duration":"","msr_version":"","msr_speaker":"","msr_other_contributors":"","msr_booktitle":"","msr_pages_string":"9216-9227","msr_chapter":"","msr_isbn":"","msr_journal":"Journal of Virology","msr_volume":"82","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\/cgi\/content\/abstract\/82\/18\/9216","msr_doi":"","msr_publication_uploader":[{"type":"url","title":"http:\/\/jvi.asm.org\/cgi\/content\/abstract\/82\/18\/9216","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\/cgi\/content\/abstract\/82\/18\/9216"}],"msr-author-ordering":[{"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":"text","value":"Hendrik Streeck","user_id":0,"rest_url":false},{"type":"text","value":"Mina John","user_id":0,"rest_url":false},{"type":"text","value":"Quentin Eichbaum","user_id":0,"rest_url":false},{"type":"text","value":"Brian L. Block","user_id":0,"rest_url":false},{"type":"text","value":"Brett Baker","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":"Martin Markowitz","user_id":0,"rest_url":false},{"type":"text","value":"Heiko Jessen","user_id":0,"rest_url":false},{"type":"text","value":"Anthony D. Kelleher","user_id":0,"rest_url":false},{"type":"text","value":"Eric Rosenberg","user_id":0,"rest_url":false},{"type":"text","value":"John Kaldor","user_id":0,"rest_url":false},{"type":"text","value":"Yuko Yuki","user_id":0,"rest_url":false},{"type":"text","value":"Mary Carrington","user_id":0,"rest_url":false},{"type":"text","value":"Todd M. Allen","user_id":0,"rest_url":false},{"type":"text","value":"Simon Mallal","user_id":0,"rest_url":false},{"type":"text","value":"Marcus Altfeld","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":"Bruce D. Walker","user_id":0,"rest_url":false}],"msr_impact_theme":[],"msr_research_lab":[],"msr_event":[],"msr_group":[144943],"msr_project":[396113],"publication":[],"video":[],"msr-tool":[240158],"msr_publication_type":"article","related_content":{"projects":[{"ID":396113,"post_title":"PhyloD","post_name":"phylod","post_type":"msr-project","post_date":"2017-07-03 15:17:56","post_modified":"2021-02-11 17:39:50","post_status":"publish","permalink":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/project\/phylod\/","post_excerpt":"HIV, like most retroviruses, is characterized by a tremendous rate of mutation, which leads to a high level of genetic diversity within and among patients. This genetic variation is the substrate for rapid within-host evolution. As our immune system learns to target the virus, the virus adapts, leading to an endless game of cat-and-mouse. From a scientific perspective, this provides a useful opportunity: if HIV is constantly adapting to our individual immune responses, then studying&hellip;","_links":{"self":[{"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-project\/396113"}]}}]},"_links":{"self":[{"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-research-item\/157460","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\/157460\/revisions"}],"predecessor-version":[{"id":446499,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-research-item\/157460\/revisions\/446499"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/media\/230089"}],"wp:attachment":[{"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/media?parent=157460"}],"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=157460"},{"taxonomy":"msr-research-area","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/research-area?post=157460"},{"taxonomy":"msr-publication-type","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-publication-type?post=157460"},{"taxonomy":"msr-publisher","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-publisher?post=157460"},{"taxonomy":"msr-focus-area","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-focus-area?post=157460"},{"taxonomy":"msr-locale","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-locale?post=157460"},{"taxonomy":"msr-post-option","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-post-option?post=157460"},{"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=157460"},{"taxonomy":"msr-conference","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-conference?post=157460"},{"taxonomy":"msr-journal","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-journal?post=157460"},{"taxonomy":"msr-impact-theme","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-impact-theme?post=157460"},{"taxonomy":"msr-pillar","embeddable":true,"href":"https:\/\/cm-edgetun.pages.dev\/en-us\/research\/wp-json\/wp\/v2\/msr-pillar?post=157460"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}