Landon Thompson, Imran Jamal, Juthika Das, Casey Dang, Zhenzi Hong, Doran Katz, Alberto Bosque, Vir B Singh
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引用次数: 0
摘要
由于多种调节潜伏机制的相互作用,消除HIV潜伏库是一项极具挑战性的任务。因此,我们需要寻找新的策略来均匀地瞄准非均质储层。最近的报道为RNA聚合酶III (RNAP III)的新型抗病毒功能提供了有趣的证据,这仍有待进一步探索。在这项研究中,我们评估了RNA Pol III在调节HIV潜伏期和复制中的作用。我们首先证明了RNAP III的药理学抑制可以导致代表T细胞和单核细胞储存库的细胞系中潜伏期的强烈再激活。接下来,我们利用HIV-1假型(DuoFluo)病毒和HIV-1- bal在THP-1和Sup-T1细胞中研究了RNA Pol III参与调节HIV-1复制的作用。我们发现RNAP III的药理学抑制显著诱导HIV转录。这些发现在生理相关的原发CD4 T细胞中得到进一步证实,并且在72小时内观察到HIV转录持续增加。总的来说,我们的研究表明,抑制RNAP III可以增加HIV转录率,而HIV总DNA保持不变。总的来说,我们的研究确定了RNA Pol III在限制HIV转录中的未知作用,并主张靶向RNAP III驱动的机制可能是一种重新激活HIV潜伏库的新策略。
RNA Polymerase III Regulates HIV Replication and Latency.
The elimination of HIV latent reservoirs is an extremely challenging task due to the interplay of multiple mechanisms regulating latency. Thus, we need to identify novel strategies to target heterogeneous reservoirs uniformly. Recent reports have provided intriguing evidence for the novel antiviral function of RNA Polymerase III (RNAP III), which remains to be further explored. In this study, we evaluated the role of RNA Pol III in regulating HIV latency and replication. We first demonstrated that the pharmacological inhibition of RNAP III can lead to a strong reactivation of latency in cell lines representing both T and monocytic cellular reservoirs. Next, we investigated the involvement of RNA Pol III in regulating HIV-1 replication using HIV-1 pseudotyped (DuoFluo) virus and HIV-1-Bal in THP-1 and Sup-T1 cells. We show that the pharmacological inhibition of RNAP III significantly induced HIV transcription. These findings were further confirmed in physiologically relevant primary CD4 T cells, and a consistent increase in HIV transcription was observed up to 72 h. Collectively, our study suggests that inhibition of RNAP III can increase the rate of HIV transcription, while the total HIV DNA remains unchanged. Overall, our study identifies a previously unknown role of RNA Pol III in restricting HIV transcription and advocates that targeting RNAP III-driven mechanisms could be a novel strategy to reactivate HIV latent reservoirs.
期刊介绍:
Viruses (ISSN 1999-4915) is an open access journal which provides an advanced forum for studies of viruses. It publishes reviews, regular research papers, communications, conference reports and short notes. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. We also encourage the publication of timely reviews and commentaries on topics of interest to the virology community and feature highlights from the virology literature in the ''News and Views'' section. Electronic files or software regarding the full details of the calculation and experimental procedure, if unable to be published in a normal way, can be deposited as supplementary material.