Porcine deltacoronavirus nonstructural protein 2 inhibits type I and III IFN production by targeting STING for degradation

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...

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Bibliographic Details
Published in:Veterinary research (Paris) 2024-06, Vol.55 (1), p.79-14
Main 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
Format: Article
Language:English
Subjects:
Animals
Coronavirus Infections - immunology
Coronavirus Infections - metabolism
Coronavirus Infections - veterinary
Coronavirus Infections - virology
Coronaviruses
Deltacoronavirus - genetics
Deltacoronavirus - physiology
Diseases
Health aspects
HEK293 Cells
Immune Evasion
Immune system
Immunity, Innate
Interferon
interferon production
Interferon Type I - genetics
Interferon Type I - metabolism
Life Sciences
Membrane Proteins - genetics
Membrane Proteins - metabolism
nonstructural protein 2
Physiological aspects
Porcine deltacoronavirus
STING
Swine
Swine Diseases - immunology
Swine Diseases - virology
Ubiquitination
Viral Nonstructural Proteins - genetics
Viral Nonstructural Proteins - metabolism
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Summary: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.
ISSN:0928-4249
1297-9716
1297-9716
DOI:10.1186/s13567-024-01330-w