HSF1 Activation Can Restrict HIV Replication
Name
nihms-1615699.pdf
Description
Accepted version
Size
1.74 MB
Format
Adobe PDF
Checksum (MD5)
39079a973b9a0cc1bb291a4326df9a37
Author(s)
Nekongo, Emmanuel E
Ponomarenko, Anna I
Dewal, Mahender B
Butty, Vincent L
Browne, Edward P
Shoulders, Matthew D
Date Issued
2020
Journal
ACS Infectious Diseases
Publisher
American Chemical Society (ACS)
Version
Author's final manuscript
Abstract
Copyright © 2020 American Chemical Society. 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.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1021/ACSINFECDIS.0C00166
