数字农科院2.0

Duck enteritis virus protein kinase US3 inhibits DNA sensing signaling by phosphorylating interferon regulatory factor 7

文献类型： 外文期刊

作者： Rui Liu;Li Gao;Fuchun Yang;Xiaohan Li;Changjun Liu;Xiaole Qi;Hongyu Cui;Yanping Zhang;Suyan Wang;Xiaomei Wang;Yulong Gao;Kai Li

关键词： Duck enteritis virus; DNA sensing; interferon regulatory factor 7; US3

期刊名称： Microbiology Spectrum

ISSN： 2165-0497

年卷期： 2022 年

页码：

收录情况： SCIE（2022版）

摘要： The cytosolic DNA sensing pathway mediates innate immune defense against infection by many DNA viruses; however, viruses have evolved multiple strategies to evade the host immune response. Duck enteritis virus (DEV) causes an acute and contagious disease with high mortality in waterfowl. The mechanisms employed by DEV to block DNA sensing pathway are not well understood. Here, we sought to investigate the role of DEV US3, a serine/threonine protein kinase, in the inhibition of DNA sensing. We found that ectopic expression of DEV US3 significantly inhibited the production of IFN-β and expression of interferon-stimulated genes induced by interferon-stimulatory DNA and poly(dA:dT ). US3 also inhibited viral DNA-triggered IFN-β activation and promoted DEV replication in duck embryo fibroblasts, while knockdown of US3 during DEV infection enhances the IFN-β response and suppresses viral replication. US3 inhibited the DNA-sensing signaling pathway by targeting interferon regulatory factor 7 (IRF7), and the kinase activity of US3 was indispensable for its inhibitory function. Furthermore, we found that US3 interacts with the activation domain of IRF7, phosphorylating IRF7, blocking its dimerization and nuclear translocation, and finally leading to the inhibition of IFN-β production. These findings expand our knowledge on DNA sensing in ducks and reveal a novel mechanism whereby DEV evades host antiviral immunity.

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