HSF1 Activation Can Restrict HIV Replication

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.