| 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 |
