HSF1 Activation Can Restrict HIV Replication
HSF1 Activation Can Restrict HIV Replication
复制标题
DOI：
10.1021/acsinfecdis.0c00166
复制
发表时间：
2020-07-10
影响因子：
5.3
通讯作者：
Shoulders, Matthew D.
中科院分区：
文献类型：
--
作者：
Nekongo, Emmanuel E.;Ponomarenko, Anna, I;Shoulders, Matthew D.
宿主蛋白折叠应激反应在RNA病毒的复制和进化中起着重要作用。先前的研究表明，胞质调节因子热休克因子1（HSF 1）和人类免疫缺陷病毒-1（HIV-1）之间存在复杂的相互作用。我们试图将HSF 1转录因子活性与细胞毒性蛋白质稳态应激分离，从而更好地阐明HSF 1在HIV-1生命周期中的作用。为了实现这一目标，我们使用化学遗传学，压力独立控制HSF 1活性，以确定HSF 1是否以及如何影响HIV-1复制。应激非依赖性HSF 1诱导降低了HIV-1病毒粒子的总量和感染性。此外，HIV-1在几次连续传代过程中无法逃脱HSF 1介导的限制。这些结果阐明了宿主的热休克反应和HIV-1感染之间的相互作用，并激发了对分子伴侣作为潜在的抗病毒治疗靶点的持续研究。
Host protein folding stress responses can play important roles in RNA virus replication and evolution. Prior work suggested a complicated interplay between the cytosolic regulator heat shock factor 1 (HSF1), and human immunodeficiency virus-1 (HIV-1). We sought to uncouple HSF1 transcription factor activity from cytotoxic proteostasis stress and thereby better elucidate the proposed role(s) of HSF1 in the HIV-1 lifecycle. To achieve this objective, we used chemical genetic, stress-independent control of HSF1 activity to establish whether and how HSF1 influences HIV-1 replication. Stress-independent HSF1 induction decreased both the total quantity and infectivity of HIV-1 virions. Moreover, HIV-1 was unable to escape HSF1-mediated restriction over the course of several serial passages. These results clarify the interplay between the host's heat shock response and HIV-1 infection and motivate continued investigation of chaperones as potential antiviral therapeutic targets.