Stromal Antigen 2 Deficiency Induces Interferon Responses and Restricts Porcine Deltacoronavirus Infection

Yang Wu; Hongling Zhang; Jianfei Chen; Zhaorong Shi; Mingwei Li; Ying Zhao; Hongyan Shi; Da Shi; Longjun Guo; Li Feng

doi:10.3390/v14081783

Stromal Antigen 2 Deficiency Induces Interferon Responses and Restricts Porcine Deltacoronavirus Infection

Viruses. 2022 Aug 15;14(8):1783. doi: 10.3390/v14081783.

Authors

Yang Wu¹, Hongling Zhang¹, Jianfei Chen¹, Zhaorong Shi¹, Mingwei Li¹, Ying Zhao¹, Hongyan Shi¹, Da Shi¹, Longjun Guo¹, Li Feng¹

Affiliation

¹ State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001, China.

Abstract

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.

Keywords: PDCoV; STAG2; interferon signaling pathway; replication.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antiviral Agents / metabolism
Coronavirus Infections*
Coronavirus* / physiology
Deltacoronavirus
Interferons / metabolism
Swine
Swine Diseases*

Substances

Antiviral Agents
Interferons

Supplementary concepts

Porcine coronavirus HKU15

Grants and funding

The research was supported by the National Key R&D Program of China (2021YFD1801105), the National Natural Science Foundation of China (31872474), the Natural Science Foundation of Heilongjiang Province of China (YQ2020C023), and the Central Public-interest Scientific Institution Basal Research Fund (no.1610302020001).