Rare HIV-1 transmitted/founder lineages identified by deep viral sequencing contribute to rapid shifts in dominant quasispecies during acute and early infection.
Rare HIV-1 transmitted/founder lineages identified by deep viral sequencing contribute to rapid shifts in dominant quasispecies during acute and early infection.
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DOI：
10.1371/journal.ppat.1006510
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发表时间：
2017-07
期刊：
影响因子：
6.7
通讯作者：
Kim JH
中科院分区：
文献类型：
--
作者：
Kijak GH;Sanders-Buell E;Chenine AL;Eller MA;Goonetilleke N;Thomas R;Leviyang S;Harbolick EA;Bose M;Pham P;Oropeza C;Poltavee K;O'Sullivan AM;Billings E;Merbah M;Costanzo MC;Warren JA;Slike B;Li H;Peachman KK;Fischer W;Gao F;Cicala C;Arthos J;Eller LA;O'Connell RJ;Sinei S;Maganga L;Kibuuka H;Nitayaphan S;Rao M;Marovich MA;Krebs SJ;Rolland M;Korber BT;Shaw GM;Michael NL;Robb ML;Tovanabutra S;Kim JH
了解急性HIV-1感染（AHI）过程中发生的事件，对于合理设计HIV-1防治干预措施具有重要意义。我们对来自早期捕获急性感染RV 217队列的6名参与者进行了病毒深度测序，研究了在病毒血症出现后的前几周内每周两次收集的血浆中的HIV-1演变。对多重传播/创始（T/F）病毒确定的感染进行分析，发现了新的病毒特征，包括：a）次要T/F变异体的低水平持续性，B）次要T/F快速取代主要T/F，c）次要T/F的初始扩增，随后相同次要T/F快速崩溃至低频率。在大多数参与者中，细胞毒性T淋巴细胞（CTL）逃逸首先在病毒血症高峰期结束时检测到，以高于以前在HIV-1感染中测量的速率进行，并且通常通过探索表位内的多个突变途径发生。CTL逃逸变体的快速出现表明强烈的和早期的CTL应答。较小的T/F病毒株可以有助于在AHI期间HIV-1准种进化的快速和多样的概况。总的来说，我们的研究结果表明，早期，深入，频繁的采样是必要的，以调查病毒/宿主相互作用在AHI，这可能有助于确定预防和治愈HIV-1感染的先决条件。开发安全、有效和可扩展的疫苗和治疗策略来控制HIV-1大流行是一个主要的公共卫生问题。这些预防和治疗措施的合理设计需要对病毒感染后最初几周内HIV-1与其宿主之间的相互作用有深刻的了解（即，急性感染）。在这里，我们进行了一个系统的和深入的研究，个人的感染前检测到病毒血症高峰和出现的第一个抗体反应。在急性感染期间每周两次收集血浆样本，我们对病毒群进行了下一代测序。在大多数参与者中，我们首先检测到病毒从最初的适应性细胞免疫反应中逃逸，在病毒血症高峰下降的末期。病毒逃逸的速度比以前在HIV-1感染中测量的速度更高，通常是通过探索多种突变途径。对多个病毒谱系建立的感染序列的分析显示，构成每个宿主体内HIV-1群体的病毒频率发生了巨大变化。这些结果，使用早期，深度和频繁的采样，支持快速变化的病毒谱系可能在适应性细胞免疫和可能的其他宿主反应在急性HIV-1感染。
In order to inform the rational design of HIV-1 preventive and cure interventions it is critical to understand the events occurring during acute HIV-1 infection (AHI). Using viral deep sequencing on six participants from the early capture acute infection RV217 cohort, we have studied HIV-1 evolution in plasma collected twice weekly during the first weeks following the advent of viremia. The analysis of infections established by multiple transmitted/founder (T/F) viruses revealed novel viral profiles that included: a) the low-level persistence of minor T/F variants, b) the rapid replacement of the major T/F by a minor T/F, and c) an initial expansion of the minor T/F followed by a quick collapse of the same minor T/F to low frequency. In most participants, cytotoxic T-lymphocyte (CTL) escape was first detected at the end of peak viremia downslope, proceeded at higher rates than previously measured in HIV-1 infection, and usually occurred through the exploration of multiple mutational pathways within an epitope. The rapid emergence of CTL escape variants suggests a strong and early CTL response. Minor T/F viral strains can contribute to rapid and varied profiles of HIV-1 quasispecies evolution during AHI. Overall, our results demonstrate that early, deep, and frequent sampling is needed to investigate viral/host interaction during AHI, which could help identify prerequisites for prevention and cure of HIV-1 infection. The development of safe, effective, and scalable vaccines and cure strategies to control the HIV-1 pandemic is a major public health concern. The rational design of these preventive and treatment measures requires a profound knowledge of the interaction between HIV-1 and its host during the first weeks that follow viral infection (i.e., acute infection). Here we performed a systematic and in-depth study of individuals whose infection was detected before peak viremia and before the emergence of the first antibody responses. Plasma samples were collected twice weekly during acute infection and we performed next-generation sequencing of the viral swarms. In most participants, we first detected viral escape from the initial adaptive cellular immune responses at the end of peak viremia downslope. Viral escape proceeded at higher rates than previously measured in HIV-1 infection and usually through the exploration of multiple mutational pathways. The analysis of sequences from infections established by multiple viral lineages revealed dramatic shifts in the frequencies of the viruses that composed the HIV-1 population within each host. These results, using early, deep, and frequent sampling, support rapidly changing viral lineages likely in response to both adaptive cellular immunity and possibly other host responses during acute HIV-1 infection.
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影响因子：
3.7
作者：
Chenine AL;Wieczorek L;Sanders-Buell E;Wesberry M;Towle T;Pillis DM;Molnar S;McLinden R;Edmonds T;Hirsch I;O'Connell R;McCutchan FE;Montefiori DC;Ochsenbauer C;Kappes JC;Kim JH;Polonis VR;Tovanabutra S
通讯作者：
Tovanabutra S
影响因子：
11.1
作者：
Ananworanich, Jintanat;Chomont, Nicolas;Eller, Leigh Ann;Kroon, Eugene;Tovanabutra, Sodsai;Bose, Meera;Nau, Martin;Fletcher, James L. K.;Tipsuk, Somporn;Vandergeeten, Claire;O'Connell, Robert J.;Pinyakorn, Suteeraporn;Michael, Nelson;Phanuphak, Nittaya;Robb, Merlin L.
通讯作者：
Robb, Merlin L.
DOI：
10.1086/655653
发表时间：
2010-10-15
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Boutwell CL;Rolland MM;Herbeck JT;Mullins JI;Allen TM
通讯作者：
Allen TM
DOI：
10.1126/science.1254031
发表时间：
2014-07-11
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Carlson JM;Schaefer M;Monaco DC;Batorsky R;Claiborne DT;Prince J;Deymier MJ;Ende ZS;Klatt NR;DeZiel CE;Lin TH;Peng J;Seese AM;Shapiro R;Frater J;Ndung'u T;Tang J;Goepfert P;Gilmour J;Price MA;Kilembe W;Heckerman D;Goulder PJ;Allen TM;Allen S;Hunter E
通讯作者：
Hunter E
影响因子：
4.3
作者：
Edlefsen PT;Rolland M;Hertz T;Tovanabutra S;Gartland AJ;deCamp AC;Magaret CA;Ahmed H;Gottardo R;Juraska M;McCoy C;Larsen BB;Sanders-Buell E;Carrico C;Menis S;Kijak GH;Bose M;RV144 Sequencing Team;Arroyo MA;O'Connell RJ;Nitayaphan S;Pitisuttithum P;Kaewkungwal J;Rerks-Ngarm S;Robb ML;Kirys T;Georgiev IS;Kwong PD;Scheffler K;Pond SL;Carlson JM;Michael NL;Schief WR;Mullins JI;Kim JH;Gilbert PB
通讯作者：
Gilbert PB