Single-Cell Analysis of Quiescent HIV Infection Reveals Host Transcriptional Profiles that Regulate Proviral Latency
Single-Cell Analysis of Quiescent HIV Infection Reveals Host Transcriptional Profiles that Regulate Proviral Latency
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DOI：
10.1016/j.celrep.2018.09.020
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发表时间：
2018-10-02
期刊：
影响因子：
8.8
通讯作者：
Browne, Edward P.
中科院分区：
文献类型：
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作者：
Bradley, Todd;Ferrari, Guido;Browne, Edward P.
详细了解建立或维持HIV潜伏库的机制将指导消除持续感染的方法。我们使用HIV潜伏期的细胞系和原代细胞模型，使用单细胞方法研究病毒RNA （vRNA）的表达和宿主转录组的作用。单细胞vRNA定量鉴定了表达不同水平vRNA的不同细胞群体，包括完全沉默的群体。引人注目的是，潜伏感染原代细胞的单细胞rna测序表明，HIV下调发生在不同的转录组环境中，但与一组特定细胞基因的表达显著相关。特别是，潜伏期在表达转录特征的细胞中更常见，这些转录特征包括幼稚T细胞和中枢记忆T细胞的标记。这些数据表明潜伏库中HIV前病毒的表达受到宿主细胞转录程序的影响。这些程序的治疗调节可以逆转或加强HIV潜伏期。
A detailed understanding of the mechanisms that establish or maintain the latent reservoir of HIV will guide approaches to eliminate persistent infection. We used a cell line and primary cell models of HIV latency to investigate viral RNA (vRNA) expression and the role of the host transcriptome using single-cell approaches. Single-cell vRNA quantitation identified distinct populations of cells expressing various levels of vRNA, including completely silent populations. Strikingly, single-cell RNA-seq of latently infected primary cells demonstrated that HIV down-regulation occurred in diverse transcriptomic environments but was significantly associated with expression of a specific set of cellular genes. In particular, latency was more frequent in cells expressing a transcriptional signature that included markers of naive and central memory T cells. These data reveal that expression of HIV proviruses within the latent reservoir are influenced by the host cell transcriptional program. Therapeutic modulation of these programs may reverse or enforce HIV latency.