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DDX5 inhibits type I IFN production by promoting degradation of TBK1 and disrupting formation of TBK1 − TRAF3 complex

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Abstract

DExD/H-box helicase (DDX) 5 belongs to the DExD/H-box helicase family. DDX family members play differential roles in the regulation of innate antiviral immune response. However, whether DDX5 is involved in antiviral immunity remains unclear. In this study, we found that DDX5 serves as a negative regulator of type I interferon (IFN) response. Overexpression of DDX5 inhibited IFN production induced by Spring viremia of carp virus (SVCV) and poly(I:C) and enhanced virus replication by targeting key elements of the RLR signaling pathway (MAVS, MITA, TBK1, IRF3 and IRF7). Mechanistically, DDX5 directly interacted with TBK1 to promote its autophagy-mediated degradation. Moreover, DDX5 was shown to block the interaction between TRAF3 and TBK1, hence preventing nuclear translocation of IRF3. Together, these data shed light on the roles of DDX5 in regulating IFN response.

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Acknowledgements

The authors thank Dr Mingxian Chang for providing SVCV.

Funding

This work is funded by the National Natural Science Foundation of China (32030112 and U21A20268).

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Authors and Affiliations

  1. Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, Shanghai, 201306, China

    Yanwei Zhang, Jing Cen, Gaoliang Yuan, Zhao Jia, Kangyong Chen, Wa Gao, Jing Chen & Jun Zou

  2. International Research Center for Marine Biosciences, Ministry of Science and Technology, Shanghai Ocean University, Shanghai, 201306, China

    Yanwei Zhang, Jing Cen, Gaoliang Yuan, Zhao Jia, Kangyong Chen, Wa Gao, Jing Chen & Jun Zou

  3. National Demonstration Center for Experimental Fisheries Science Education, Shanghai Ocean University, Shanghai, 201306, China

    Yanwei Zhang, Jing Cen, Gaoliang Yuan, Zhao Jia, Kangyong Chen, Wa Gao, Jing Chen & Jun Zou

  4. Fish Disease Research Unit, Institute for Parasitology, University of Veterinary Medicine Hannover, Hannover, Germany

    Mikolaj Adamek

  5. Heilongjiang River Fisheries Research Institute, CAFS, Harbin, 150070, Heilongjiang Province, China

    Zhiying Jia

  6. Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266200, China

    Jun Zou

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  1. Yanwei Zhang
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Contributions

YZ: investigation, methodology, data curation, writing original draft. Jing Cen, GY, ZJ, KC, WG, Jing Chen: investigation, methodology. MA, ZJ: methodology, materials, manuscript editing. JZ: conceptualization, funding acquisition, project administration, supervision, review and editing.

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Correspondence to Jun Zou.

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Zhang, Y., Cen, J., Yuan, G. et al. DDX5 inhibits type I IFN production by promoting degradation of TBK1 and disrupting formation of TBK1 − TRAF3 complex. Cell. Mol. Life Sci. 80, 212 (2023). https://doi.org/10.1007/s00018-023-04860-2

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