Clones of infected cells arise early in HIV-infected individuals
Clones of infected cells arise early in HIV-infected individuals
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DOI：
10.1172/jci.insight.128432
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发表时间：
2019-06-20
期刊：
影响因子：
8
通讯作者：
Hughes, Stephen H.
中科院分区：
文献类型：
--
作者：
Coffin, John M.;Wells, David W.;Hughes, Stephen H.
在接受长期抗逆转录病毒治疗（ART）的艾滋病毒感染者中，超过40%的感染细胞是克隆的。尽管在长期抗逆转录病毒治疗的个体中存在的大多数HIV前病毒是有缺陷的，包括那些在克隆扩增细胞中的HIV前病毒，但越来越多的证据表明，在长期抗逆转录病毒治疗的患者中，携带具有复制能力的前病毒的克隆是常见的，并且构成了HIV库的一部分，这使得仅用目前的抗逆转录病毒治疗HIV感染是不可能的。鉴于克隆扩增在HIV持久性中的重要性，我们确定了HIV获得后感染的克隆多长时间可以长到足以被检测到（大于约1 x 10(5)个细胞的克隆）。我们研究了12名早期HIV感染者（Fiebig III-V/VI期）和5名慢性感染者。最近感染的个体在诊断时或接近诊断时开始接受抗逆转录病毒治疗。我们从外周血单核细胞中分离出6500多个独立的整合位点，这些位点在抗逆转录病毒治疗开始前和抑制性抗逆转录病毒治疗0.5-18年之后。一些受感染的克隆在感染艾滋病毒约4周后可被检测到，其中一些克隆可持续数年。这些结果有助于解释储层是如何早期形成并持续多年的。
In HIV-infected individuals on long-term antiretroviral therapy (ART), more than 40% of the infected cells are in clones. Although most HIV proviruses present in individuals on long-term ART are defective, including those in clonally expanded cells, there is increasing evidence that clones carrying replication-competent proviruses are common in patients on long-term ART and form part of the HIV reservoir that makes it impossible to cure HIV infection with current ART alone. Given the importance of clonal expansion in HIV persistence, we determined how soon after HIV acquisition infected clones can grow large enough to be detected (clones larger than ca. 1 x 10(5) cells). We studied 12 individuals sampled in early HIV infection (Fiebig stage III-V/VI) and 5 who were chronically infected. The recently infected individuals were started on ART at or near the time of diagnosis. We isolated more than 6,500 independent integration sites from peripheral blood mononuclear cells before ART was initiated and after 0.5-18 years of suppressive ART. Some infected clones could be detected approximately 4 weeks after HIV infection and some of these clones persisted for years. The results help to explain how the reservoir is established early and persists for years.