Porcine deltacoronavirus nucleocapsid protein species-specifically suppressed IRF7-induced type I interferon production via ubiquitin-proteasomal degradation pathway

Coronaviruses (CoVs) is showing obvious interspecies transmission, such as the SARS-CoV, MERS-CoV and SARS-CoV-2 Here, the emerging porcine deltacoronavirus (PDCoV) strain, isolated from Shanghai, China, broadly infects porcine, human and chicken cells in vitro Previously studies by our group and others have confirmed that PDCoV nucleocapsid (N) protein performs an important role in antagonizing retinoic acid-induced gene I-like receptor (RLR) activation However, the mechanism of PDCoV N protein suppressing porcine type I IFN production remains unclear, especially the downstream of porcine RLR signaling pathway In the present study, porcine IRF7 (poIRF7) was identified as the interaction protein of PDCoV N protein through LC-MS/MS The poIRF7 (268-487aa) was the key region of binding PDCoV N protein Although IRF7 is a conserved functional protein in species, the PDCoV N protein has been confirmed to interact with only poIRF7 and significantly decrease poIRF7-induced type I IFN production, but not human or chicken IRF7 Furthermore, PDCoV N protein can promote poIRF7 degradation via the ubiquitin-proteasome pathway, which directly increased the K6, K11, and K29-linked polyubiquitination of poIRF7 Lysine 359 of poIRF7 was a key site in PDCoV N protein inducing poIRF7 degradation Taken together, our results reveal a novel mechanism that PDCoV N protein could species-specifically interact with poIRF7 and then promote its degradation to suppress porcine type I IFN production The novel findings provide a new insight into PDCoV and other zoonotic coronavirus evading the innate immune response of different species