Quantitative deep sequencing reveals dynamic HIV-1 escape and large population shifts during CCR5 antagonist therapy in vivo.
Quantitative deep sequencing reveals dynamic HIV-1 escape and large population shifts during CCR5 antagonist therapy in vivo.
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定量深度测序揭示了体内 CCR5 拮抗剂治疗期间 HIV-1 的动态逃逸和大规模群体变化。
DOI：
10.1371/journal.pone.0005683
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发表时间：
2009-05-25
期刊：
影响因子：
3.7
通讯作者：
Kuritzkes DR
中科院分区：
文献类型：
--
作者：
Tsibris AM;Korber B;Arnaout R;Russ C;Lo CC;Leitner T;Gaschen B;Theiler J;Paredes R;Su Z;Hughes MD;Gulick RM;Greaves W;Coakley E;Flexner C;Nusbaum C;Kuritzkes DR
高通量测序平台提供了一种检测罕见 HIV-1 变异并更全面记录准种多样性的方法。我们将该技术应用于从 4 名慢性 HIV 感染者收集的样本中 env 的 V3 环编码区，这些受试者的 CCR5 拮抗剂（vicriviroc [VVC]）治疗失败。每个样本获得 25,000–140,000 个扩增序列。存在深刻的基线 V3 环序列异质性；预测的 CXCR4 使用人群在主要使用 CCR5 的人群中得到鉴定。与随后的病毒学失败相关的 V3 环形式（通过 CXCR4 的使用或高水平 VVC 耐药性的出现）以微小变异的形式出现，占基线样本的 0.8-2.8%。群体频率向这些形式发生了极端、快速的转变，深度测序提供了 VVC 选择的快速进化影响的详细视图。选择后观察到更大的 V3 多样性。这种先前未报道的 V3 环序列多样性程度对病毒发病机制、疫苗设计和 HIV-1 CCR5 拮抗剂的最佳使用具有影响。
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.
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影响因子：
3.8
作者：
Low, Andrew J.;Dong, Winnie;Harrigan, P. Richard
通讯作者：
Harrigan, P. Richard
影响因子：
56.9
作者：
HWANG, SS;BOYLE, TJ;CULLEN, BR
通讯作者：
CULLEN, BR
影响因子：
56.9
作者：
COFFIN, JM
通讯作者：
COFFIN, JM
DOI：
10.1073/pnas.0811713106
发表时间：
2009-03-31
影响因子：
11.1
作者：
Anastassopoulou, Cleo G.;Ketas, Thomas J.;Moore, John P.
通讯作者：
Moore, John P.
影响因子：
4.9
作者：
Strizki, JM;Tremblay, C;Baroudy, BM
通讯作者：
Baroudy, BM