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A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3
Published on: January 24, 2016
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ERRα negatively regulates type I interferon induction by inhibiting TBK1-IRF3 interaction
Xiang He1, Shengli Ma1, Yinyin Tian1,2
1State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology, Beijing, P.R. China.
Plos Pathogens
|June 8, 2017
Summary
Estrogen-related receptor alpha (ERRα) deficiency enhances resistance to viral infections. ERRα inhibits type-I interferon production and antiviral gene expression, making it a potential therapeutic target.
Area of Science:
- Immunology
- Molecular Biology
- Virology
Background:
- Estrogen-related receptor alpha (ERRα), a nuclear receptor, regulates energy homeostasis.
- The role of ERRα in antiviral innate immunity is not fully understood.
Purpose of the Study:
- To investigate the role of ERRα in antiviral innate immunity.
- To identify ERRα as a potential target for antiviral therapies.
Main Methods:
- In vivo and in vitro viral infection models.
- Analysis of type-I interferon (IFN-I) production and interferon-stimulated genes (ISGs).
- Investigation of ERRα interaction with TBK1 and IRF3 signaling pathways.
Main Results:
- ERRα deficiency conferred resistance to viral infection.
- ERRα inhibited IFN-I production and ISG expression.
- Viral infection stabilized ERRα, which interfered with TBK1-IRF3 complex formation, IRF3 phosphorylation, dimerization, and DNA binding.
- ERRα's inhibitory effect was independent of transcriptional activity and PCG-1α.
- The ERRα inhibitor XCT790 demonstrated broad antiviral activity.
Conclusions:
- ERRα acts as a critical negative regulator of antiviral innate immunity.
- Targeting ERRα with inhibitors like XCT790 may offer a novel antiviral therapeutic strategy.
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