| Autor: |
Athe M N Tsibris, Bette Korber, Ramy Arnaout, Carsten Russ, Chien-Chi Lo, Thomas Leitner, Brian Gaschen, James Theiler, Roger Paredes, Zhaohui Su, Michael D Hughes, Roy M Gulick, Wayne Greaves, Eoin Coakley, Charles Flexner, Chad Nusbaum, Daniel R Kuritzkes |
| Jazyk: |
angličtina |
| Rok vydání: |
2009 |
| Předmět: |
|
| Zdroj: |
PLoS ONE, Vol 4, Iss 5, p e5683 (2009) |
| Druh dokumentu: |
article |
| ISSN: |
1932-6203 |
| DOI: |
10.1371/journal.pone.0005683 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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