Measuring replication competent HIV-1: advances and challenges in defining the latent reservoir.

Measuring replication competent HIV-1: advances and challenges in defining the latent reservoir.
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DOI:
10.1186/s12977-018-0404-7
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发表时间:
2018-02-13
期刊:
影响因子:
3.3
通讯作者:
Laird GM
Laird GM
中科院分区:
医学2区
文献类型:
--
作者:
Wang Z;Simonetti FR;Siliciano RF;Laird GM

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抗逆转录病毒疗法不能治愈HIV-1感染,因为少数潜伏感染的细胞携带有复制能力的前病毒。测量持久的HIV-1是具有挑战性的,因为它由缺陷和完整的前病毒的镶嵌群体组成,这些前病毒可以从潜伏状态转变为活跃的HIV-1转录。由于这种复杂性,目前的大多数检测方法检测到多种类型的持久性HIV-1,导致对潜在宿主的真实大小估计过高。在这里,我们回顾了病毒生长试验的发展,这是复制能力前病毒的黄金标准量化,并讨论了全长HIV-1基因组测序方法提供的洞察力,使我们能够解开前病毒的组成。在这篇综述中,我们剖析了是什么定义了HIV-1的持久性,并检查了未得到满足的需求,以衡量旨在消除HIV-1宿主的干预措施的有效性。
Antiretroviral therapy cannot cure HIV-1 infection due to the persistence of a small number of latently infected cells harboring replication-competent proviruses. Measuring persistent HIV-1 is challenging, as it consists of a mosaic population of defective and intact proviruses that can shift from a state of latency to active HIV-1 transcription. Due to this complexity, most of the current assays detect multiple categories of persistent HIV-1, leading to an overestimate of the true size of the latent reservoir. Here, we review the development of the viral outgrowth assay, the gold-standard quantification of replication-competent proviruses, and discuss the insights provided by full-length HIV-1 genome sequencing methods, which allowed us to unravel the composition of the proviral landscape. In this review, we provide a dissection of what defines HIV-1 persistence and we examine the unmet needs to measure the efficacy of interventions aimed at eliminating the HIV-1 reservoir.
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