EGR1 Suppresses Porcine Epidemic Diarrhea Virus Replication by Regulating IRAV To Degrade Viral Nucleocapsid Protein
Hua Wang, Ning Kong, Yajuan Jiao, Sujie Dong, Dage Sun, Xiaoyong Chen, Hao Zheng, Tong Wu, Hai Yu, Lingxue Yu, Wen Zhang, Guangzhi Tong, Tongling Shan
Abstract
PEDV is a highly contagious enteric coronavirus that has rapidly emerged worldwide and has caused severe economic losses. No currently available drugs or vaccines can effectively control PEDV. PEDV has evolved many strategies to limit IFN-I production. We identified EGR1 as a novel host restriction factor and demonstrated that EGR1 suppresses PEDV replication by directly binding to the IRAV promoter and upregulating the expression of IRAV, which interacts with and degrades the PEDV N protein via the E3 ubiquitin ligase MARCH8 to catalyze nucleocapsid protein ubiquitination, which adds another layer of complexity to the innate antiviral immunity of this newly identified restriction factor. A better understanding of the innate immune response to PEDV infection will aid the development of novel therapeutic targets and more effective vaccines against virus infection.