African Swine Fever Virus E120R Protein Inhibits Interferon Beta Production by Interacting with IRF3 To Block Its Activation
Huisheng Liu, Zixiang Zhu, Tao Feng, Zhao Ma, Xue Qiao, Panxue Wu, Li Pan, Shasha Li, Fan Yang, Weijun Cao, Zhaoning Xue, Hongjun Chen, Xiangtao Liu, Haixue Zheng
Abstract
African swine fever is a highly contagious animal disease affecting the pig industry worldwide, which has brought enormous economic losses. Infection by the causative agent, African swine fever virus (ASFV), causes severe immunosuppression during viral infection, contributing to serious clinical manifestations. Therefore, identification of the viral proteins involved in immunosuppression is critical for ASFV vaccine design and development. Here, for the first time, we demonstrated that E120R protein, a structural protein of ASFV, played an important role in suppression of interferon regulatory factor 3 (IRF3) phosphorylation and type I interferon production by binding to IRF3 and blocking the recruitment of IRF3 to TANK-binding kinase 1 (TBK1). Deletion of the crucial binding sites in E120R critically increased the interferon response during ASFV infection. This study explored a novel antagonistic mechanism of ASFV, which is critical for guiding the development of ASFV live-attenuated vaccines.