Quantitative deep sequencing reveals dynamic HIV-1 escape and large population shifts during CCR5 antagonist therapy in vivo

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Quantitative deep sequencing reveals dynamic HIV-1 escape and large population shifts during CCR5 antagonist therapy in vivo

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dc.contributor.author Korber, Bette
dc.contributor.author Russ, Carsten
dc.contributor.author Lo, Chien-Chi
dc.contributor.author Leitner, Thomas
dc.contributor.author Gaschen, Brian
dc.contributor.author Theiler, James
dc.contributor.author Paredes, Roger
dc.contributor.author Su, Zhaohui
dc.contributor.author Gulick, Roy M.
dc.contributor.author Greaves, Wayne
dc.contributor.author Coakley, Eoin
dc.contributor.author Flexner, Charles
dc.contributor.author Nusbaum, Chad
dc.contributor.author Tsibris, Athe Michael Noel
dc.contributor.author Arnaout, Ramy
dc.contributor.author Hughes, Michael David
dc.contributor.author Kuritzkes, Daniel Robert
dc.date.accessioned 2011-04-23T18:42:50Z
dc.date.issued 2009
dc.identifier.citation Tsibris, Athe M. N., Bette Korber, Ramy Arnaout, Carsten Russ, Chien-Chi Lo, Thomas Leitner, Brian Gaschen, et al. 2009. Quantitative deep sequencing reveals dynamic HIV-1 escape and large population shifts during CCR5 antagonist therapy in vivo. PLoS ONE 4(5): e5683. en_US
dc.identifier.issn 1932-6203 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:4874827
dc.description.abstract High-throughput sequencing platforms provide an approach for detecting rare HIV-1 variants and documenting more fully quasispecies diversity. We applied this technology to the V3 loop-coding region of env in samples collected from 4 chronically HIV-infected subjects in whom CCR5 antagonist (vicriviroc [VVC]) therapy failed. Between 25,000–140,000 amplified sequences were obtained per sample. Profound baseline V3 loop sequence heterogeneity existed; predicted CXCR4-using populations were identified in a largely CCR5-using population. The V3 loop forms associated with subsequent virologic failure, either through CXCR4 use or the emergence of high-level VVC resistance, were present as minor variants at 0.8–2.8% of baseline samples. Extreme, rapid shifts in population frequencies toward these forms occurred, and deep sequencing provided a detailed view of the rapid evolutionary impact of VVC selection. Greater V3 diversity was observed post-selection. This previously unreported degree of V3 loop sequence diversity has implications for viral pathogenesis, vaccine design, and the optimal use of HIV-1 CCR5 antagonists. en_US
dc.language.iso en_US en_US
dc.publisher Public Library of Science en_US
dc.relation.isversionof doi:10.1371/journal.pone.0005683 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2682648/pdf/ en_US
dash.license LAA
dc.subject genetics and genomics en_US
dc.subject microbial evolution and genomics en_US
dc.subject virology en_US
dc.subject host invasion and cell entry en_US
dc.subject mechanisms of resistance and susceptibility, including host genetics en_US
dc.subject virus evolution and symbiosis en_US
dc.subject infectious diseases en_US
dc.subject HIV infection and AIDS en_US
dc.title Quantitative deep sequencing reveals dynamic HIV-1 escape and large population shifts during CCR5 antagonist therapy in vivo en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal PLoS ONE en_US
dash.depositing.author Tsibris, Athe Michael Noel
dc.date.available 2011-04-23T18:42:50Z
dash.affiliation.other HMS^Medicine-Massachusetts General Hospital en_US
dash.affiliation.other HMS^Pathology en_US
dash.affiliation.other HMS^Medicine-Brigham and Women's Hospital en_US

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