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Viruses 2019, 11(2), 158; https://doi.org/10.3390/v11020158

THO Complex Subunit 7 Homolog Negatively Regulates Cellular Antiviral Response against RNA Viruses by Targeting TBK1

1
Key Laboratory of Functional Small Organic Molecules, Ministry of Education and College of Life Science, Jiangxi Normal University, 99 Ziyang Avenue, Nanchang 330022, Jiangxi, China
2
Department of Anesthesiology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA
*
Authors to whom correspondence should be addressed.
Co-first authors.
Received: 7 December 2018 / Revised: 5 February 2019 / Accepted: 12 February 2019 / Published: 15 February 2019
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Abstract

RNA virus invasion induces a cytosolic RIG-I-like receptor (RLR) signaling pathway by promoting assembly of the Mitochondrial antiviral-signaling protein (MAVS) signalosome and triggers the rapid production of type I interferons (IFNs) and proinflammatory cytokines. During this process, the pivotal kinase TANK binding kinase 1 (TBK1) is recruited to the MAVS signalosome to transduce a robust innate antiviral immune response by phosphorylating transcription factors interferon regulatory factor 3 (IRF3) and nuclear factor (NF)-κB and promoting their nuclear translocation. However, the molecular mechanisms underlying the negative regulation of TBK1 are largely unknown. In the present study, we found that THO complex subunit 7 homolog (THOC7) negatively regulated the cellular antiviral response by promoting the proteasomal degradation of TBK1. THOC7 overexpression potently inhibited Sendai virus- or polyI:C-induced IRF3 dimerization and phosphorylation and IFN-β production. In contrast, THOC7 knockdown had the opposite effects. Moreover, we simulated a node-activated pathway to show that THOC7 regulated the RIG-I-like receptors (RLR)-/MAVS-dependent signaling cascade at the TBK1 level. Furthermore, THOC7 was involved in the MAVS signalosome and promoted TBK1 degradation by increasing its K48 ubiquitin-associated polyubiquitination. Together, these findings suggest that THOC7 negatively regulates type I IFN production by promoting TBK1 proteasomal degradation, thus improving our understanding of innate antiviral immune responses. View Full-Text
Keywords: THOC7; MAVS signalosome; TBK1; cellular antiviral response THOC7; MAVS signalosome; TBK1; cellular antiviral response
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He, T.-S.; Xie, T.; Li, J.; Yang, Y.-X.; Li, C.; Wang, W.; Cao, L.; Rao, H.; Ju, C.; Xu, L.-G. THO Complex Subunit 7 Homolog Negatively Regulates Cellular Antiviral Response against RNA Viruses by Targeting TBK1. Viruses 2019, 11, 158.

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