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
| Title: | Quantitative deep sequencing reveals dynamic HIV-1 escape and large population shifts during CCR5 antagonist therapy in vivo |
| Author: |
Korber, Bette; Russ, Carsten; Lo, Chien-Chi; Leitner, Thomas; Gaschen, Brian; Theiler, James; Paredes, Roger; Su, Zhaohui; Gulick, Roy M.; Greaves, Wayne; Coakley, Eoin; Flexner, Charles; Nusbaum, Chad; Tsibris, Athe Michael Noel; Arnaout, Ramy; Hughes, Michael David; Kuritzkes, Daniel Robert
Note: Order does not necessarily reflect citation order of authors. |
| 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. |
| Full Text & Related Files: |
2682648.pdf (881.2Kb; PDF) 
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| 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. |
| Published Version: | doi:10.1371/journal.pone.0005683 |
| Other Sources: | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2682648/pdf/ |
| Terms of Use: | This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA |
| Citable link to this page: | http://nrs.harvard.edu/urn-3:HUL.InstRepos:4874827 |
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