Restriction of V3 region sequence divergence in the HIV-1 envelope gene during antiretroviral treatment in a cohort of recent seroconverters.
Restriction of V3 region sequence divergence in the HIV-1 envelope gene during antiretroviral treatment in a cohort of recent seroconverters.
复制标题
DOI：
10.1186/1742-4690-10-8
复制
发表时间：
2013-01-18
期刊：
影响因子：
3.3
通讯作者：
SPARTAC Trial Investigators
中科院分区：
文献类型：
--
作者：
Gall A;Kaye S;Hué S;Bonsall D;Rance R;Baillie GJ;Fidler SJ;Weber JN;McClure MO;Kellam P;SPARTAC Trial Investigators
人类免疫缺陷病毒1 （HIV-1）序列多样性和分化的动态变化与原发性感染和艾滋病进展期间的免疫控制有关。HIV-1包膜（env）基因的共识测序或单基因组扩增测序，特别是可变(V)区域，被用作HIV-1基因组多样性的标记，但使用这些方法只能最小限度地或半定量地采样群体多样性。在这里，我们使用第二代深度测序来确定患者之间和患者内部的序列异质性，并量化在血清转化后接受或未接受抗逆转录病毒治疗的个体队列中的微小变异；SPARTAC试验。我们通过对30例初次感染抗逆转录病毒患者env V3序列多样性的横断面研究表明，存在相当大的群体结构多样性，其中一些个体表现出高度受限的血浆病毒多样性。多样性与感染的临床标志物（病毒载量、血清转化时间、CD4细胞计数）无关。对未接受治疗的个体进行超过60周的连续采样，确定了三种最初不同的多样性概况，表明可以很容易地检测到持续的HIV-1序列多样化和分化的复杂模式。从这一分析中可以推断出次要序列更替、新变体的出现和存档变体的重新出现的证据。在接受短疗程（12周，ART12）或长疗程抗逆转录病毒治疗（48周，ART48）的患者和未接受治疗的对照组中，同一时间段的病毒分化分析显示，ART48成功抑制了病毒分化，而ART12没有显著效果。作为HIV-1基因组多样性的重要组成部分，深度测序是研究env V3多样性的一种敏感可靠的方法。在antiretroviral-naïve最近的服务器转换器中，详细了解了复杂的早期患者内部env V3多样性和分化动态。长期抗逆转录病毒治疗，在血清转化后不久开始并给予48周，可显著限制HIV-1分化。目前在SPARTAC试验中正在研究ART12和ART48对HIV感染和进展的临床标志物的影响。
Dynamic changes in Human Immunodeficiency Virus 1 (HIV-1) sequence diversity and divergence are associated with immune control during primary infection and progression to AIDS. Consensus sequencing or single genome amplification sequencing of the HIV-1 envelope (env) gene, in particular the variable (V) regions, is used as a marker for HIV-1 genome diversity, but population diversity is only minimally, or semi-quantitatively sampled using these methods. Here we use second generation deep sequencing to determine inter-and intra-patient sequence heterogeneity and to quantify minor variants in a cohort of individuals either receiving or not receiving antiretroviral treatment following seroconversion; the SPARTAC trial. We show, through a cross-sectional study of sequence diversity of the env V3 in 30 antiretroviral-naive patients during primary infection that considerable population structure diversity exists, with some individuals exhibiting highly constrained plasma virus diversity. Diversity was independent of clinical markers (viral load, time from seroconversion, CD4 cell count) of infection. Serial sampling over 60 weeks of non-treated individuals that define three initially different diversity profiles showed that complex patterns of continuing HIV-1 sequence diversification and divergence could be readily detected. Evidence for minor sequence turnover, emergence of new variants and re-emergence of archived variants could be inferred from this analysis. Analysis of viral divergence over the same time period in patients who received short (12 weeks, ART12) or long course antiretroviral therapy (48 weeks, ART48) and a non-treated control group revealed that ART48 successfully suppressed viral divergence while ART12 did not have a significant effect. Deep sequencing is a sensitive and reliable method for investigating the diversity of the env V3 as an important component of HIV-1 genome diversity. Detailed insights into the complex early intra-patient dynamics of env V3 diversity and divergence were explored in antiretroviral-naïve recent seroconverters. Long course antiretroviral therapy, initiated soon after seroconversion and administered for 48 weeks, restricts HIV-1 divergence significantly. The effect of ART12 and ART48 on clinical markers of HIV infection and progression is currently investigated in the SPARTAC trial.
登录
查看更多内容
影响因子：
12.3
作者：
Huse SM;Huber JA;Morrison HG;Sogin ML;Welch DM
通讯作者：
Welch DM
影响因子：
5.4
作者：
Harrington, Patrick R.;Nelson, Julie A. E.;Swanstrom, Ronald
通讯作者：
Swanstrom, Ronald
影响因子：
1.5
作者：
Mens, Helene;Pedersen, Anders G.;Katzenstein, Terese L.
通讯作者：
Katzenstein, Terese L.
DOI：
10.1073/pnas.0804192105
发表时间：
2008-10-28
影响因子：
11.1
作者：
Joos, Beda;Fischer, Marek;Guenthard, Huldrych F.
通讯作者：
Guenthard, Huldrych F.
影响因子：
3.7
作者：
Fischer W;Ganusov VV;Giorgi EE;Hraber PT;Keele BF;Leitner T;Han CS;Gleasner CD;Green L;Lo CC;Nag A;Wallstrom TC;Wang S;McMichael AJ;Haynes BF;Hahn BH;Perelson AS;Borrow P;Shaw GM;Bhattacharya T;Korber BT
通讯作者：
Korber BT