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THO Complex Subunit 7 Homolog Negatively Regulates Cellular Antiviral Response against RNA Viruses by Targeting TBK1
Tian-Sheng He1, Tao Xie2, Jing Li3
1Key Laboratory of Functional Small Organic Molecules, Ministry of Education and College of Life Science, Jiangxi Normal University, 99 Ziyang Avenue, Nanchang 330022, Jiangxi, China. hetiansheng361@163.com.
Viruses
|February 17, 2019
Summary
THO complex subunit 7 homolog (THOC7) degrades the key antiviral kinase TBK1, inhibiting type I interferon production. This discovery clarifies negative regulation in innate antiviral immunity.
Area of Science:
- Immunology
- Molecular Biology
- Virology
Background:
- RNA virus detection triggers cytosolic RIG-I-like receptor (RLR) signaling via MAVS.
- This pathway activates type I interferons (IFNs) and inflammation through TBK1 kinase.
- Mechanisms for negative regulation of TBK1 in antiviral response remain unclear.
Purpose of the Study:
- Investigate the role of THO complex subunit 7 homolog (THOC7) in regulating antiviral immunity.
- Elucidate the molecular mechanisms by which THOC7 affects TBK1 activity and IFN production.
Main Methods:
- Overexpression and knockdown of THOC7 in cell models.
- Stimulation with Sendai virus and polyI:C.
- Analysis of IRF3 dimerization/phosphorylation, IFN-β production, and TBK1 degradation.
- Ubiquitination assays and signalosome complex analysis.
Main Results:
- THOC7 overexpression inhibited RLR-mediated IFN-β production and IRF3 activation.
- THOC7 knockdown enhanced antiviral responses.
- THOC7 directly interacts with MAVS and promotes TBK1 proteasomal degradation via K48-linked ubiquitination.
- THOC7 acts as a negative regulator at the TBK1 level.
Conclusions:
- THOC7 negatively regulates type I IFN production by promoting TBK1 proteasomal degradation.
- THOC7's role in TBK1 ubiquitination and degradation sheds light on innate antiviral immune response regulation.
- Findings enhance understanding of the molecular basis of antiviral immunity.
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