SADS‐CoV nsp1 inhibits the IFN‐β production by preventing TBK1 phosphorylation and inducing CBP degradation

Swine acute diarrhea syndrome (SADS) is first reported in January 2017 in Southern China. It subsequently causes widespread outbreaks in multiple pig farms, leading to economic losses. Therefore, it is an urgent to understand the molecular mechanisms underlying the pathogenesis and immune evasion of Swine acute diarrhea syndrome coronavirus (SADS‐CoV). Our research discovered that SADS‐CoV inhibited the production of interferon‐β (IFN‐β) during viral infection. The nonstructural protein 1 (nsp1) prevented the phosphorylation of TBK1 by obstructing the interaction between TBK1 and Ub protein. Moreover, nsp1 induced the degradation of CREB‐binding protein (CBP) through the proteasome‐dependent pathway, thereby disrupting the IFN‐β enhancer and inhibiting IFN transcription. Finally, we identified nsp1‐Phe39 as the critical amino acid that downregulated IFN production. In conclusion, our findings described two mechanisms in nsp1 that inhibited IFN production and provided new insights into the evasion strategy adopted by SADS‐CoV to evade host antiviral immunity.