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Journal of General Virology header logo Journal of General Virology

Volume 104, Issue 8

Inhibition of salt inducible kinases reduces rhythmic HIV-1 replication and reactivation from latency Open Access

Abstract

Human immunodeficiency virus type 1 (HIV-1) causes a major burden on global health, and eradication of latent virus infection is one of the biggest challenges in the field. The circadian clock is an endogenous timing system that oscillates with a ~24 h period regulating multiple physiological processes and cellular functions, and we recently reported that the cell intrinsic clock regulates rhythmic HIV-1 replication. Salt inducible kinases (SIK) contribute to circadian regulatory networks, however, there is limited evidence for SIKs regulating HIV-1 infection. Here, we show that pharmacological inhibition of SIKs perturbed the cellular clock and reduced rhythmic HIV-1 replication in circadian synchronised cells. Further, SIK inhibitors or genetic silencing of expression inhibited viral replication in primary cells and in a latency model, respectively. Overall, this study demonstrates a role for salt inducible kinases in regulating HIV-1 replication and latency reactivation, which can provide innovative routes to better understand and target latent HIV-1 infection.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): circadian rhythms , HIV-1 , host-pathogen interactions and salt inducible kinases
Funding
This study was supported by the:
  • Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases (Award UM1-AI-164567)
    • Principle Award Recipient: PersephoneBorrow
  • Chinese Academy of Medical Sciences Initiative for Innovative Medicine (Award 2018-I2M-2-002)
    • Principle Award Recipient: JaneA McKeating
  • Medical Research Foundation (Award MR/R022011/1)
    • Principle Award Recipient: JaneA McKeating
  • Wellcome Trust (Award 200838/Z/16/Z)
    • Principle Award Recipient: JaneA McKeating
  • Indonesia Endowment Fund for Education
    • Principle Award Recipient: DiniIsmed
  • Wellcome Trust (Award 108869/Z/15/Z)
    • Principle Award Recipient: BorrmannHelene
© 2023 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2023-08-02
2025-01-15
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Inhibition of salt inducible kinases reduces rhythmic HIV-1 replication and reactivation from latency
J. Gen. Virol. 104, 001877 (2023); https://doi.org/10.1099/jgv.0.001877
/content/journal/jgv/10.1099/jgv.0.001877
/content/journal/jgv/10.1099/jgv.0.001877
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