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 |
dc.identifier.doi | 10.1371/journal.pone.0005683 | * |
dash.authorsordered | false | |
dash.contributor.affiliated | Tsibris, Athe | |
dash.contributor.affiliated | Hughes, Michael | |
dash.contributor.affiliated | Arnaout, Ramy | |
dash.contributor.affiliated | Kuritzkes, Daniel | |