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Updated: Jun 23, 2025
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Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation
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Transcription factor EB (TFEB) interaction with RagC is disrupted during enterovirus D68 infection
Alagie Jassey1, Noah Pollack1, Michael A Wagner1
1Department of Microbiology and Immunology and Center for Pathogen Research, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Journal of Virology
|June 18, 2024
Summary
Transcription factor EB (TFEB) is essential for Enterovirus D68 replication and spread. EV-D68 protease cleaves TFEB, disrupting its function and promoting viral release, suggesting TFEB as an antiviral target.
Area of Science:
- Virology
- Molecular Biology
- Cell Biology
Background:
- Enterovirus D68 (EV-D68) causes severe respiratory illness and acute flaccid myelitis.
- No vaccines or antivirals currently exist for EV-D68.
- EV-D68 utilizes cellular autophagy pathways for replication.
Purpose of the Study:
- To investigate the role of transcription factor EB (TFEB) in EV-D68 infection.
- To elucidate the mechanism by which EV-D68 interacts with TFEB.
- To identify TFEB as a potential antiviral target.
Main Methods:
- TFEB knockdown experiments to assess its impact on viral replication.
- Analysis of TFEB cleavage by EV-D68 3C protease.
- Overexpression of TFEB mutants to study its role in viral egress and autophagy.
- Experiments in autophagy-defective cells.
Main Results:
- TFEB knockdown reduced EV-D68 genomic RNA replication but not viral entry.
- EV-D68 3C protease cleaves TFEB, disrupting its interaction with RagC and lysosomal transport.
- TFEB cleavage and subsequent cytosolic localization are crucial for EV-D68 nonlytic release.
- A TFEB mutant lacking the RagC-binding domain inhibited autophagy and enhanced viral egress.
Conclusions:
- TFEB is a critical host factor for multiple stages of the EV-D68 lifecycle.
- EV-D68 manipulates TFEB function through protease cleavage to facilitate viral replication and egress.
- Targeting TFEB presents a promising strategy for developing novel antiviral therapies against EV-D68.
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