Host protein folding stress responses can play important roles in RNA virus replication and evolution. Prior work suggested a complicated interplay between the cytosolic proteostasis stress response, controlled by the transcriptional master 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.

中文翻译：

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HSF1激活可以限制HIV复制。

宿主蛋白折叠应激反应可以在RNA病毒复制和进化中发挥重要作用。先前的工作表明，受转录主调节因子热休克因子1（HSF1）和人类免疫缺陷病毒1（HIV-1）控制的胞浆蛋白稳态压力反应之间存在复杂的相互作用。我们试图使HSF1转录因子活性与细胞毒性蛋白稳态压力解偶联，从而更好地阐明HSF1在HIV-1生命周期中的拟议作用。为了实现此目标，我们使用了化学遗传学，不受压力的HSF1活性控制来确定HSF1是否以及如何影响HIV-1复制。不依赖压力的HSF1诱导降低了HIV-1病毒体的总量和感染力。此外，在多次连续传代过程中，HIV-1无法逃脱HSF1介导的限制。这些结果阐明了宿主的热休克反应与HIV-1感染之间的相互作用，并激发了对伴侣蛋白作为潜在抗病毒治疗靶标的持续研究。