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A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3
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Beta-coronaviruses exploit cellular stress responses by modulating TFEB and TFE3 activity

Pablo S Contreras1, Pablo J Tapia1, Eutteum Jeong1

  • 1Cell and Developmental Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.

Iscience
|February 14, 2023
PubMed

Insights

Transcription factors TFEB and TFE3 move to the nucleus during beta-coronavirus infection, regulating immune responses and cellular survival. This highlights their crucial role in host defense against these viruses.

Area of Science:

  • Virology
  • Cell Biology
  • Immunology

Background:

  • Beta-coronaviruses pose significant global health risks.
  • Understanding host-pathogen interactions is key for developing effective treatments.

Purpose of the Study:

  • To investigate the role of transcription factors TFEB and TFE3 in the cellular response to beta-coronavirus infection.
  • To elucidate the mechanism of TFEB and TFE3 nuclear translocation and their downstream effects.

Main Methods:

  • Studied nuclear translocation of TFEB and TFE3 upon beta-coronavirus infection.
  • Investigated the role of calcineurin phosphatase in this process.
  • Analyzed the binding of TFEB/TFE3 to lysosomal and immune gene promoters.
  • Assessed immune gene expression in TFEB/TFE3-depleted and over-expressed cells.

Main Results:

  • TFEB and TFE3 translocate to the nucleus via calcineurin activation during infection.
  • These factors bind to promoters of lysosomal and immune genes.
  • Depletion of TFEB/TFE3 reduces immune gene upregulation and viral infectivity.
  • Over-expression of TFEB/TFE3 increases cytokine and chemokine expression.

Conclusions:

  • TFEB and TFE3 play a central role in the cellular response to beta-coronavirus infection.
  • Their nuclear translocation influences immune gene expression, lysosomal function, and viral infectivity.
  • These findings offer insights into host-pathogen dynamics and potential therapeutic targets.
Keywords:
Molecular biologyVirology

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