%0 Journal Article
%T Porcine deltacoronavirus nonstructural protein 2 inhibits type I and III IFN production by targeting STING for degradation.
%A Liu X
%A Ji L
%A Cheng Y
%A Kong L
%A Xie S
%A Yang J
%A Chen J
%A Wang Z
%A Ma J
%A Wang H
%A Yan Y
%A Sun J
%J Vet Res
%V 55
%N 1
%D 2024 Jun 17
%M 38886840
%F 3.829
%R 10.1186/s13567-024-01330-w
%X Porcine deltacoronavirus (PDCoV) is an enteropathogenic coronavirus that has been reported to use various strategies to counter the host antiviral innate immune response. The cGAS-STING signalling pathway plays an important role in antiviral innate immunity. However, it remains unclear whether PDCoV achieves immune evasion by regulating the cGAS-STING pathway. Here, we demonstrated that the nonstructural protein 2 (nsp2) encoded by PDCoV inhibits cGAS-STING-mediated type I and III interferon (IFN) responses via the regulation of porcine STING (pSTING) stability. Mechanistically, ectopically expressed PDCoV nsp2 was found to interact with the N-terminal region of pSTING. Consequently, pSTING was degraded through K48-linked ubiquitination and the proteasomal pathway, leading to the disruption of cGAS-STING signalling. Furthermore, K150 and K236 of pSTING were identified as crucial residues for nsp2-mediated ubiquitination and degradation. In summary, our findings provide a basis for elucidating the immune evasion mechanism of PDCoV and will contribute to the development of targets for anti-coronavirus drugs.