{Reference Type}: Journal Article
{Title}: Porcine deltacoronavirus nonstructural protein 2 inhibits type I and III IFN production by targeting STING for degradation.
{Author}: Liu X;Ji L;Cheng Y;Kong L;Xie S;Yang J;Chen J;Wang Z;Ma J;Wang H;Yan Y;Sun J;
{Journal}: Vet Res
{Volume}: 55
{Issue}: 1
{Year}: 2024 Jun 17
{Factor}: 3.829
{DOI}: 10.1186/s13567-024-01330-w
{Abstract}: 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.