IFN-β1b induces OAS3 to inhibit EV71 via IFN-β1b/JAK/STAT1 pathway

Baisong Zheng; Xiaolei Zhou; Li Tian; Jian Wang; Wenyan Zhang

doi:10.1016/j.virs.2022.07.013

October 2022

Citation: Baisong Zheng, Xiaolei Zhou, Li Tian, Jian Wang, Wenyan Zhang. IFN-β1b induces OAS3 to inhibit EV71 via IFN-β1b/JAK/STAT1 pathway .VIROLOGICA SINICA, 2022, 37(5) : 676-684. http://dx.doi.org/10.1016/j.virs.2022.07.013

IFN-β1b induces OAS3 to inhibit EV71 via IFN-β1b/JAK/STAT1 pathway

Center for Pathogen Biology and Infectious Diseases, Institute of Virology and AIDS Research, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, The First Hospital of Jilin University, Changchun, 130021, China

Corresponding author: Wenyan Zhang, zhangwenyan@jlu.edu.cn
Received Date: 21 January 2022
Accepted Date: 27 July 2022
Available online: 05 August 2022

Abstract

Enterovirus 71 (EV71) caused hand, foot and mouth disease (HFMD) is a serious threat to the health of young children. Although type I interferon (IFN-I) has been proven to control EV71 replication, the key downstream IFN-stimulated gene (ISG) remains to be clarified and investigated. Recently, we found that 2'-5'-oligoadenylate synthetases 3 (OAS3), as one of ISG of IFN-β1b, was antagonized by EV71 3C protein. Here, we confirm that OAS3 is the major determinant of IFN-β1b-mediated EV71 inhibition, which depends on the downstream constitutive RNase L activation. 2'-5'-oligoadenylate (2-5A) synthesis activity deficient mutations of OAS3 D816A, D818A, D888A, and K950A lost resistance to EV71 because they could not activate downstream RNase L. Further investigation proved that EV71 infection induced OAS3 but not RNase L expression by IFN pathway. Mechanically, EV71 or IFN-β1b-induced phosphorylation of STAT1, but not STAT3, initiated the transcription of OAS3 by directly binding to the OAS3 promoter. Our works elucidate the immune regulatory mechanism of the host OAS3/RNase L system against EV71 replication.
- Enterovirus 71 (EV71)
- , 2'-5'-oligoadenylate synthetases 3 (OAS3)
- , RNase L
- , IFN-β1b
- , JAK/STAT

Electronic Supplementary Material

10.1016j.virs.2022.07.013-ESM.docx
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