A quantitative approach for measuring the reservoir of latent HIV-1 proviruses
A quantitative approach for measuring the reservoir of latent HIV-1 proviruses
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DOI：
10.1038/s41586-019-0898-8
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发表时间：
2019-02-07
期刊：
影响因子：
64.8
通讯作者：
Siliciano, Robert F.
中科院分区：
文献类型：
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作者：
Bruner, Katherine M.;Wang, Zheng;Siliciano, Robert F.
HIV-1在静息CD 4（+）T细胞中的稳定潜伏库是治愈的主要障碍（1-3）。靶向储层的治疗策略正在测试中（4，5），需要准确、可扩展的储层测定。储库是通过对在一轮T细胞活化后释放感染性病毒的细胞进行定量病毒生长测定来定义的（1）。然而，这些定量生长测定和活化后产生病毒RNA的细胞的较新测定（6）可能低估了储存库的大小，因为一轮活化不会诱导所有前病毒（7）。许多研究依赖于基于聚合酶链反应的简单测定来检测前病毒DNA，而不管转录状态如何，但是这些测定的临床相关性尚不清楚，因为绝大多数前病毒是有缺陷的（7-9）。在这里，我们描述了一个更准确的方法来测量HIV-1水库，分别量化完整和有缺陷的前病毒。我们发现，在体外和体内的细胞，携带完整和有缺陷的前病毒的动力学是不同的。这些发现对靶向完整的前病毒具有意义，前病毒是治疗HIV感染的障碍。
A stable latent reservoir for HIV-1 in resting CD4(+) T cells is the principal barrier to a cure(1-3). Curative strategies that target the reservoir are being tested(4,5) and require accurate, scalable reservoir assays. The reservoir was defined with quantitative viral outgrowth assays for cells that release infectious virus after one round of T cell activation(1). However, these quantitative outgrowth assays and newer assays for cells that produce viral RNA after activation(6) may underestimate the reservoir size because one round of activation does not induce all proviruses(7). Many studies rely on simple assays based on polymerase chain reaction to detect proviral DNA regardless of transcriptional status, but the clinical relevance of these assays is unclear, as the vast majority of proviruses are defective(7-9). Here we describe a more accurate method of measuring the HIV-1 reservoir that separately quantifies intact and defective proviruses. We show that the dynamics of cells that carry intact and defective proviruses are different in vitro and in vivo. These findings have implications for targeting the intact proviruses that are a barrier to curing HIV infection.