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A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3
Published on: January 24, 2016
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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
Summary
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.
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