PDF(Pubmed)
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.
摘要：
猪三角洲冠状病毒（PDCoV）是一种肠致病性冠状病毒，据报道可以使用各种策略来对抗宿主抗病毒先天性免疫反应。cGAS-STING信号通路在抗病毒先天免疫中起重要作用。然而,目前尚不清楚PDCoV是否通过调节cGAS-STING途径实现免疫逃避.这里,我们证明了PDCoV编码的非结构蛋白2（nsp2）通过调节猪STING（pSTING）稳定性来抑制cGAS-STING介导的I型和III型干扰素（IFN）反应。机械上,发现异位表达的PDCoVnsp2与pSTING的N端区域相互作用。因此,pSTING通过K48连接的泛素化和蛋白酶体途径降解，导致cGAS-STING信号中断。此外，pSTING的K150和K236被鉴定为nsp2介导的泛素化和降解的关键残基。总之,我们的发现为阐明PDCoV的免疫逃避机制提供了基础,并将有助于开发抗冠状病毒药物的靶点.
