State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001, China.
Viruses. 2022 Aug 15;14(8):1783. doi: 10.3390/v14081783.
Porcine deltacoronavirus (PDCoV) is a recently discovered enteropathogenic coronavirus and has caused significant economic impacts on the pork industry. Although studies have partly uncovered the molecular mechanism of PDCoV-host interaction, it requires further research. In this study, we explored the roles of Stromal Antigen 2 (STAG2) in PDCoV infection. We found that STAG2-deficient cells inhibited infection with vesicular stomatitis virus (VSV) and PDCoV, whereas restoration of STAG2 expression in STAG2-depleted (STAG2) IPEC-J2 cells line restored PDCoV infection, suggesting that STAG2 is involved in the PDCoV replication. Furthermore, we found that STAG2 deficiency results in robust interferon (IFN) expression. Subsequently, we found that STAG2 deficiency results in the activation of JAK-STAT signaling and the expression of IFN stimulated gene (ISG), which establish an antiviral state. Taken together, the depletion of STAG2 activates the JAK-STAT signaling and induces the expression of ISG, thereby inhibiting PDCoV replication. Our study provides new insights and potential therapeutic targets for unraveling the mechanism of PDCoV replication.
猪德尔塔冠状病毒（PDCoV）是一种新近发现的肠致病性冠状病毒，已对养猪业造成重大经济影响。尽管研究已经部分揭示了 PDCoV 与宿主相互作用的分子机制，但仍需要进一步研究。在本研究中，我们探讨了基质抗原 2（STAG2）在 PDCoV 感染中的作用。我们发现，STAG2 缺陷细胞抑制了水疱性口炎病毒（VSV）和 PDCoV 的感染，而在 STAG2 耗尽（STAG2）IPEC-J2 细胞系中恢复 STAG2 的表达则恢复了 PDCoV 的感染，表明 STAG2 参与了 PDCoV 的复制。此外，我们发现 STAG2 缺陷导致干扰素（IFN）的强烈表达。随后，我们发现 STAG2 缺陷导致 JAK-STAT 信号的激活和 IFN 刺激基因（ISG）的表达，从而建立抗病毒状态。综上所述，STAG2 的耗竭激活了 JAK-STAT 信号，并诱导了 ISG 的表达，从而抑制了 PDCoV 的复制。我们的研究为揭示 PDCoV 复制的机制提供了新的见解和潜在的治疗靶点。
