DDX56 inhibits type I interferon by disrupting assembly of IRF3-IPO5 to inhibit IRF3 nucleus import

J Cell Sci. 2019 Jul 24;133(5):jcs230409. doi: 10.1242/jcs.230409.

Dan Li ¹, Shaozu Fu ¹, Zhengqian Wu ¹, Wenping Yang ¹, Yi Ru ¹, Hongbing Shu ², Xiangtao Liu ¹, Haixue Zheng ³

Affiliations

1 State Key Laboratory of Veterinary Etiological Biology and OIE/National Foot and Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu 730046, China.
2 Medical Research Institute, Wuhan University, Wuhan 430072, China.
3 State Key Laboratory of Veterinary Etiological Biology and OIE/National Foot and Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu 730046, China [email protected].

Abstract

Transcription factor IRF3-mediated type I interferon induction plays a role in Antiviral innate immunity. However, mechanisms for the control and regulation of IRF3 nuclear import remain largely unknown. We have identified DEAD box polypeptide 56 (DDX56) as a negative regulator of virus-triggered IFN-β induction. Overexpression of DDX56 suppressed nuclear translocation of IRF3 via disrupting the IRF3-IOP5 interaction, whereas knockdown or knockout of DDX56 had the opposite effect. In addition, the interaction between DDX56 and IRF3 increased during viral Infection. We further found that the D166 site of DDX56 was essential for inhibiting IRF3 import into the nucleus. Our findings suggest that DDX56 regulates Antiviral innate immunity by inhibiting the nuclear translocation of IRF3, revealing a novel mechanism of the DDX56-mediated innate Antiviral response.This article has an associated First Person interview with the first author of the paper.

Keywords

DDX56; IPO5; IRF3; Nucleus import; Type I interferon.

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