SADS-CoV Nsp1 hijacks proteasomal subunits to degrade IRF1.

Swine Acute Diarrhea Syndrome Coronavirus (SADS-CoV) is an emerging porcine enteric coronavirus that causes severe diarrhea in piglets. Type III interferon (IFN) are crucial for intestinal antiviral defense, and the capacity of SADS-CoV to disrupt IFN-III responses is critical for its replication. This study found that SADS-CoV inhibits IFN-III production through its nonstructural protein 1 (Nsp1), which degrades interferon regulatory factor 1 (IRF1) by promoting its ubiquitination and proteasomal degradation. Mass spectrometry and co-immunoprecipitation analyses revealed that SADS-CoV Nsp1 interacts with proteasomal subunits. Further research indicates that PSMB4, PSMB5, and PSMC5 are key proteasomal subunits involved in SADS-CoV Nsp1-induced IRF1 degradation. Similarly, Porcine Epidemic Diarrhea Virus (PEDV) and Transmissible Gastroenteritis Virus (TGEV) Nsp1 exhibit similar functions, highlighting the conserved role of coronavirus Nsp1 in immune evasion. Collectively, our findings uncover a new mechanism where SADS-CoV Nsp1 exploits the proteasome to degrade IRF1, countering IFN-III responses.