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HSF1 Activation Can Restrict HIV Replication.

Emmanuel E Nekongo1, Anna I Ponomarenko1, Mahender B Dewal1

  • 1Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.

ACS Infectious Diseases
|June 6, 2020
PubMed
Summary
This summary is machine-generated.

Heat shock factor 1 (HSF1) restricts human immunodeficiency virus-1 (HIV-1) replication and infectivity. This study clarifies the role of HSF1 in HIV-1 infection, suggesting chaperones as potential antiviral targets.

Keywords:
cytosolic proteostasisheat shock factor 1 (HSF1)heat shock response (HSR)human immunodeficiency virus-1 (HIV-1)protein folding and assembly

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Area of Science:

  • Virology
  • Molecular Biology
  • Cellular Stress Responses

Background:

  • Host protein folding stress responses are crucial for RNA virus replication.
  • Heat shock factor 1 (HSF1) regulates cytosolic proteostasis and has a complex relationship with human immunodeficiency virus-1 (HIV-1).

Purpose of the Study:

  • To investigate the specific role of HSF1 in the HIV-1 lifecycle, independent of general proteostasis stress.
  • To determine if HSF1 activity directly impacts HIV-1 replication and virion production.

Main Methods:

  • Utilized chemical genetics for stress-independent control of HSF1 activity.
  • Assessed the impact of HSF1 induction on HIV-1 replication and virion characteristics.
  • Performed serial passages of HIV-1 under HSF1-controlled conditions.

Main Results:

  • Stress-independent HSF1 activation significantly reduced HIV-1 virion quantity and infectivity.
  • HIV-1 did not develop resistance to HSF1-mediated restriction during serial passages.
  • HSF1 acts as a restriction factor for HIV-1 replication.

Conclusions:

  • HSF1 plays a direct inhibitory role in HIV-1 replication, independent of cytotoxic stress.
  • These findings elucidate the interaction between the host heat shock response and HIV-1.
  • Chaperones, regulated by HSF1, represent promising targets for novel antiviral therapies against HIV-1.