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

Author:

Liu Xiqian1,Sun Jianhe1ORCID,Yan Yaxian1,Ji Likai2,Cheng Yuqiang1,Kong Linghe1,Xie Songhua1,Yang Juan1,chen Jiaqi1,Wang Zhaofei1,Ma Jingjiao1,wang Hengan1

Affiliation:

1. Shanghai Jiao Tong University

2. Jiangsu University

Abstract

Abstract

Porcine deltacoronavirus (PDCoV) is an enteropathogenic coronavirus that has reported to employ various strategies to counter host antiviral innate immune responses. The cGAS-STING signaling 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 demonstrate that the nonstructural protein 2 (nsp2) derived from PDCoV inhibits cGAS-STING-mediated type I and III interferon (IFN) responses via regulation of porcine STING (pSTING) stability. Mechanistically, PDCoV nsp2 was found to interact with N-terminal region pSTING. Consequently, pSTING undergoes degradation through K48-linked ubiquitination and proteasomal pathway, leading to the disruption of cGAS-STING signaling. Furthermore, K150 and K236 of pSTING were identified as crucial residues for nsp2-mediated ubiquitination and degradation. In summary, our findings will provide a basis for elucidating the immune evasion mechanism of PDCOV and will contribute to the development of targets for anti-coronavirus drugs.

Publisher

Research Square Platform LLC

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