Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a recently discovered enteric coronavirus that has caused considerable economic losses in the pig industry. SADS-CoV was first reported in 2017 in Guangdong Province, China, and subsequently in Fujian, Guangxi, Henan and Jiangxi Provinces. Bone marrow stromal cell antigen 2 (BST-2), also known as tetherin, acts as an antiviral protein to limit the release of a wide range of enveloped viruses. However, the relationship between BST-2 and SADS-CoV has rarely been studied. Here, we showed that endogenous BST-2 expression is downregulated by SADS-CoV infection in Vero-E6 and ST cells by 2- to 3-fold. The overexpression of BST-2 inhibited SADS-CoV replication, whereas the knockdown of the BST-2 gene in Vero cells restored SADS-CoV replication. Further study revealed that BST-2 targets the SADS-CoV nucleocapsid protein (N) and decreases N protein expression, and that the BST-2 transmembrane (TM) domain is essential for this activity. Moreover, the degradation of the SADS-CoV N protein promoted by BST-2 is mediated by the membrane-associated ring-CH-type finger 8 (MARCHF8)/calcium binding and coiled-coil domain 2 (NDP52) autophagosome pathway. Overall, we found that BST-2 suppresses viral proliferation by inducing the breakdown of the SADS-CoV N protein via the MARCHF8/NDP52 pathway.
Chenchen Zhao,Yan Qin,Haixin Huang,Wei Chen,Yanqing Hu,Xinyu Zhang,Yuying Li,Tian Lan,Wenchao Sun
Simple SummarySADS-CoV is a newly emerging coronavirus affecting the swine industry worldwide. However, our understanding of its pathogenic pathways remains limited. In this study, the researchers aimed to determine the role of the host factor, poly(A)-binding protein 4 (PABPC4), in SADS-CoV infection. This study found that PABPC4 inhibits SADS-CoV replication by degrading the nucleocapsid protein through selective autophagy. This discovery could potentially contribute to developing novel antiviral strategies to prevent and control SADS-CoV infections, protecting the pig industry from significant economic losses.Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a novel enteric coronavirus that causes severe clinical diarrhea and intestinal pathological injury in pigs. Selective autophagy is an important mechanism of host defense against virus invasion. However, the mechanism through which SADS-CoV-mediated selective autophagy mediates the innate immune response remains unknown. Here, we report that the host protein PABPC4 can inhibit SADS-CoV replication through targeting and degrading its N protein. Furthermore, we demonstrate that PABPC4 recruits MARCHF8 (an E3 ubiquitin ligase), which ubiquitinates the N protein and is degraded via NDP52/CALCOCO2 (a selective autophagy cargo receptor). Taken together, these findings reveal a new mechanism by which PABPC4 inhibits virus replication, and reveal a new target for antiviral drug development.
危险品化学品经营许可证（带存储）