AUTHOR=Yin Mengge , Wen Wei , Wang Haoyuan , Zhao Qiongqiong , Zhu Hechao , Chen Huanchun , Li Xiangmin , Qian Ping TITLE=Porcine Sapelovirus 3Cpro Inhibits the Production of Type I Interferon JOURNAL=Frontiers in Cellular and Infection Microbiology VOLUME=Volume 12 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2022.852473 DOI=10.3389/fcimb.2022.852473 ISSN=2235-2988 ABSTRACT=Porcine Sapelovirus (PSV) is the causative pathogen of reproductive failure, acute diarrhoea, respiratory distress, or severe polioencephalomyelitis in swine. PSV often infects pigs with a mixture of other pathogens. Nevertheless, the pathogenicity and pathogenic mechanism of PSV infection is not fully understood, which hinders the disease prevention and control. In this study, we found that PSV was sensitive to type I interferon (IFN-). However, PSV could not activate the IFN-β promoter and induce IFN-β mRNA expression in infected 293T cells, indicating that PSV has evolved an effective mechanism to block IFN-β production. Further study showed that PSV inhibited the production of IFN- by cleaving mitochondrial anti-viral signaling (MAVS) and degrading melanoma differentiation-associated gene 5 (MDA5) and TANK-binding kinase 1 (TBK1) through viral 3Cpro. In addition, our study demonstrated that PSV 3Cpro degrades MDA5 and TBK1 through its protease activity, and cleaves MAVS through caspase pathway. Collectively, our results revealed that PSV inhibits the production of type I interferon to escape host antiviral immunity through cleaving and degrading the adaptor molecules.