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dc.contributor.authorKorber, Bette
dc.contributor.authorRuss, Carsten
dc.contributor.authorLo, Chien-Chi
dc.contributor.authorLeitner, Thomas
dc.contributor.authorGaschen, Brian
dc.contributor.authorTheiler, James
dc.contributor.authorParedes, Roger
dc.contributor.authorSu, Zhaohui
dc.contributor.authorGulick, Roy M.
dc.contributor.authorGreaves, Wayne
dc.contributor.authorCoakley, Eoin
dc.contributor.authorFlexner, Charles
dc.contributor.authorNusbaum, Chad
dc.contributor.authorTsibris, Athe Michael Noel
dc.contributor.authorArnaout, Ramy
dc.contributor.authorHughes, Michael David
dc.contributor.authorKuritzkes, Daniel Robert
dc.date.accessioned2011-04-23T18:42:50Z
dc.date.issued2009
dc.identifier.citationTsibris, 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.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4874827
dc.description.abstractHigh-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.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0005683en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2682648/pdf/en_US
dash.licenseLAA
dc.subjectgenetics and genomicsen_US
dc.subjectmicrobial evolution and genomicsen_US
dc.subjectvirologyen_US
dc.subjecthost invasion and cell entryen_US
dc.subjectmechanisms of resistance and susceptibility, including host geneticsen_US
dc.subjectvirus evolution and symbiosisen_US
dc.subjectinfectious diseasesen_US
dc.subjectHIV infection and AIDSen_US
dc.titleQuantitative deep sequencing reveals dynamic HIV-1 escape and large population shifts during CCR5 antagonist therapy in vivoen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorTsibris, Athe Michael Noel
dc.date.available2011-04-23T18:42:50Z
dash.affiliation.otherHMS^Medicine-Massachusetts General Hospitalen_US
dash.affiliation.otherHMS^Pathologyen_US
dash.affiliation.otherHMS^Medicine-Brigham and Women's Hospitalen_US
dc.identifier.doi10.1371/journal.pone.0005683*
dash.authorsorderedfalse
dash.contributor.affiliatedTsibris, Athe
dash.contributor.affiliatedHughes, Michael
dash.contributor.affiliatedArnaout, Ramy
dash.contributor.affiliatedKuritzkes, Daniel


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