High frequency of transmitted HIV-1 Gag HLA class I-driven immune escape variants but minimal immune selection over the first year of clade C infection.

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dc.contributor.authorGounder, Kaminien
dc.contributor.authorPadayachi, Nagavellien
dc.contributor.authorMann, Jaclyn Ken
dc.contributor.authorRadebe, Mopoen
dc.contributor.authorMokgoro, Mammekwaen
dc.contributor.authorvan der Stok, Maryen
dc.contributor.authorMkhize, Lungileen
dc.contributor.authorMncube, Zeneleen
dc.contributor.authorJaggernath, Manjeethaen
dc.contributor.authorReddy, Taryleeen
dc.contributor.authorWalker, Bruce Den
dc.contributor.authorNdung'u, Thumbien
dc.date.accessioned2016-01-28T10:38:34Zen
dc.date.available2016-01-28T10:38:34Zen
dc.date.epub2015-03-17en
dc.date.issued2015en
dc.description.abstractIn chronic HIV infection, CD8+ T cell responses to Gag are associated with lower viral loads, but longitudinal studies of HLA-restricted CD8+ T cell-driven selection pressure in Gag from the time of acute infection are limited. In this study we examined Gag sequence evolution over the first year of infection in 22 patients identified prior to seroconversion. A total of 310 and 337 full-length Gag sequences from the earliest available samples (median = 14 days after infection [Fiebig stage I/II]) and at one-year post infection respectively were generated. Six of 22 (27%) individuals were infected with multiple variants. There was a trend towards early intra-patient viral sequence diversity correlating with viral load set point (p = 0.07, r = 0.39). At 14 days post infection, 59.7% of Gag CTL epitopes contained non-consensus polymorphisms and over half of these (35.3%) comprised of previously described CTL escape variants. Consensus and variant CTL epitope proportions were equally distributed irrespective of the selecting host HLA allele and most epitopes remained unchanged over 12 months post infection. These data suggest that intrapatient diversity during acute infection is an indicator of disease outcome. In this setting, there is a high rate of transmitted CTL escape variants and limited immune selection in Gag during the first year of infection. These data have relevance for vaccine strategies designed to elicit effective CD8+ T cell immune responses.en
dc.description.sponsorshipThis research was supported by National Institutes of Health (NIH) grants RO1 AI067073-02 (Walker), South African NRF/DST (Ndung’u), Gates Foundation, IAVI. Partial funding was also received from the Victor Daitz Chair in HIV/TB Research and an International Early Career Scientist Award from the Howard Hughes Medical Institute to TN. KG was funded by the NIH Fogarty International Clinical Research Fellows (FICRF), Medical Research Council and K-RITH Collaborative grant award. JKM was supported by the National Research Foundation and the Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University. MR was funded by a UNESCO/L'Oréal Corporate Foundation fellowship and the Technology Innovation Agency of the Department of Science and Technology of South Africa. Open Access publication of this article has been made possible through support from the Victor Daitz Information Gateway, an initiative of the Victor Daitz Foundation and the University of KwaZulu-Natal. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en
dc.identifier.citationHigh frequency of transmitted HIV-1 Gag HLA class I-driven immune escape variants but minimal immune selection over the first year of clade C infection. 2015, 10 (3):e0119886 PLoS ONEen
dc.identifier.doi10.1371/journal.pone.0119886en
dc.identifier.issn1932-6203en
dc.identifier.journalPloS oneen
dc.identifier.pmid25781986en
dc.identifier.urihttp://hdl.handle.net/11288/595087en
dc.language.isoenen
dc.relation.urlhttp://dx.plos.org/10.1371/journal.pone.0119886en
dc.research.unitBiostatistics Uniten
dc.rightsArchived with thanks to PloS oneen
dc.subjectHIV infectionen
dc.subjectGag sequencingen
dc.subjectHIV-1 subtype C infectionen
dc.subjectTransmitteden
dc.subject.meshAdolescenten
dc.subject.meshAdulten
dc.subject.meshBase Sequenceen
dc.subject.meshFemaleen
dc.subject.meshGene Frequencyen
dc.subject.meshHIV Infectionsen
dc.subject.meshHIV-1en
dc.subject.meshHLA Antigensen
dc.subject.meshHumansen
dc.subject.meshMaleen
dc.subject.meshMiddle Ageden
dc.subject.meshMolecular Sequence Dataen
dc.subject.meshPolymorphism, Geneticen
dc.subject.meshSelection, Geneticen
dc.subject.meshgag Gene Products, Human Immunodeficiency Virusen
dc.titleHigh frequency of transmitted HIV-1 Gag HLA class I-driven immune escape variants but minimal immune selection over the first year of clade C infection.en
dc.typeArticleen
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