SADS-CoV N蛋白通过靶向STAT1蛋白进行降解，从而抑制JAK-STAT信号通路的活性。

Abstract

SADS-CoV N protein induces K48-linked ubiquitination and degrades STAT1 via the proteasome, thereby inhibiting JAK-STAT. • TRIM28 is identified as the E3 ligase recruited by the N protein to mediate STAT1 degradation. • STAT1 is downregulated by SADS-CoV, while its overexpression inhibits virus replication, confirming its antiviral role. In recent years, Swine Acute Diarrhea Syndrome Coronavirus (SADS-CoV) has attracted our attention as a new outbreak of porcine coronavirus. Reports on SADS-CoV indicate that this virus is widely involved in innate immunity, but its mechanism of involvement in antagonizing interferon signaling is still unclear. In this article, we found that the nucleocapsid protein (N) of SADS-CoV can inhibit the JAK-STAT signaling pathway mediated by IFN. Specifically, we found that N protein can degrade STAT1 through the ubiquitin proteasome pathway, and further discovered that N protein can promote K48 ubiquitination modification of STAT1. In addition, through mass spectrometry, we identified that the recruitment of E3 ligase TRIM28 by N protein promotes the degradation of STAT1. In addition, SADS-CoV infection of cells downregulates the protein expression level of STAT1, while overexpression of STAT1 inhibits the replication of SADS-CoV. The above results indicate that SADS-CoV N protein antagonizes the JAK-STAT signaling pathway by recruiting E3 ligase TRIM28 to mediate STAT1 degradation. These findings reveal a new mechanism by which SADS-CoV N protein antagonizes host innate immunity and provide us with novel strategies for antagonizing SADS-CoV.