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- Title
Porcine deltacoronavirus nonstructural protein 2 inhibits type I and III IFN production by targeting STING for degradation.
- Authors
Liu, Xiqian; Ji, Likai; Cheng, Yuqiang; Kong, Linghe; Xie, Songhua; Yang, Juan; Chen, Jiaqi; Wang, Zhaofei; Ma, Jingjiao; Wang, Hengan; Yan, Yaxian; Sun, Jianhe
- 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.
- Subjects
VIRAL nonstructural proteins; TYPE I interferons; DELTACORONAVIRUS; CORONAVIRUSES; CELLULAR signal transduction
- Publication
Veterinary Research, 2024, Vol 55, Issue 1, p1
- ISSN
0928-4249
- Publication type
Article
- DOI
10.1186/s13567-024-01330-w