1. Porcine deltacoronavirus nonstructural protein 2 inhibits type I and III IFN production by targeting STING for degradation
- Author
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Xiqian Liu, Likai Ji, Yuqiang Cheng, Linghe Kong, Songhua Xie, Juan Yang, Jiaqi Chen, Zhaofei Wang, Jingjiao Ma, Hengan Wang, Yaxian Yan, and Jianhe Sun
- Subjects
Porcine deltacoronavirus ,nonstructural protein 2 ,STING ,interferon production ,Veterinary medicine ,SF600-1100 - Abstract
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.
- Published
- 2024
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