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

Yanwei Zhang; Jing Cen; Gaoliang Yuan; Zhao Jia; Kangyong Chen; Wa Gao; Jing Chen; Mikolaj Adamek; Zhiying Jia; Jun Zou

doi:10.1007/s00018-023-04860-2

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

Cell Mol Life Sci. 2023 Jul 18;80(8):212. doi: 10.1007/s00018-023-04860-2.

Authors

Yanwei Zhang^{1

2

3}, Jing Cen^{1

2

3}, Gaoliang Yuan^{1

2

3}, Zhao Jia^{1

2

3}, Kangyong Chen^{1

2

3}, Wa Gao^{1

2

3}, Jing Chen^{1

2

3}, Mikolaj Adamek⁴, Zhiying Jia⁵, Jun Zou^{6

7

8

9}

Affiliations

¹ Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, Shanghai, 201306, China.
² International Research Center for Marine Biosciences, Ministry of Science and Technology, Shanghai Ocean University, Shanghai, 201306, China.
³ National Demonstration Center for Experimental Fisheries Science Education, Shanghai Ocean University, Shanghai, 201306, China.
⁴ Fish Disease Research Unit, Institute for Parasitology, University of Veterinary Medicine Hannover, Hannover, Germany.
⁵ Heilongjiang River Fisheries Research Institute, CAFS, Harbin, 150070, Heilongjiang Province, China.
⁶ Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, Shanghai, 201306, China. jzou@shou.edu.cn.
⁷ International Research Center for Marine Biosciences, Ministry of Science and Technology, Shanghai Ocean University, Shanghai, 201306, China. jzou@shou.edu.cn.
⁸ National Demonstration Center for Experimental Fisheries Science Education, Shanghai Ocean University, Shanghai, 201306, China. jzou@shou.edu.cn.
⁹ Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266200, China. jzou@shou.edu.cn.

PMID: 37462751
DOI: 10.1007/s00018-023-04860-2

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.

Keywords: Autophagy; CyHV3; DDX5; PLAC8; SVCV; TBK1.

MeSH terms

Antiviral Agents
Dichlorodiphenyl Dichloroethylene
Immunity, Innate
Interferon Regulatory Factor-3 / genetics
Interferon Regulatory Factor-3 / metabolism
Interferon Type I* / metabolism
Phosphorylation
Protein Serine-Threonine Kinases* / genetics
Protein Serine-Threonine Kinases* / metabolism
TNF Receptor-Associated Factor 3 / genetics
TNF Receptor-Associated Factor 3 / metabolism

Substances

Protein Serine-Threonine Kinases
TNF Receptor-Associated Factor 3
Dichlorodiphenyl Dichloroethylene
Interferon Type I
Interferon Regulatory Factor-3
Antiviral Agents

Abstract

MeSH terms

Substances

Grants and funding