Duck Tembusu Virus Inhibits Type I Interferon Production through the JOSD1-SOCS1-IRF7 Negative-Feedback Regulation Pathway
Shanzhi Huang, Juan Huang, Min Cui, Xuedong Wu, Mingshu Wang, Dekang Zhu, Shun Chen, Mafeng Liu, Xinxin Zhao, Ying Wu, Qiao Yang, Shaqiu Zhang, Xumin Ou, Sai Mao, Qun Gao, Yanling Yu, Bin Tian, Yunya Liu, Ling Zhang, Zhongqiong Yin, Bo Jing, Xiaoyue Chen, Anchun Cheng, Renyong Jia
Abstract
DTMUV is a newly discovered flavivirus that seriously harms the poultry industry. In recent years, there have been numerous studies on the involvement of ubiquitination in the regulation of innate immunity. However, little is known about the involvement of ubiquitination in the regulation of flavivirus-induced type I IFN signaling. In this study, we found that SOCS1 was induced by TLR3 signaling during DTMUV infection. Furthermore, we found for the first time that duck SOCS1 protein was also modified by K48-linked polyubiquitination, whereas our previous study found that SOCS1 was upregulated during DTMUV infection. Further studies showed that JOSD1 stabilized SOCS1 expression by mediating the deubiquitination of SOCS1. While SOCS1 acts as a negative regulator of cytokines, we found that DTMUV utilized SOCS1 to mediate the ubiquitination and proteasomal degradation of IRF7 and ultimately inhibit type I IFN production, thereby promoting its proliferation.