2′, 5′-Oligoadenylate Synthetase 2 (OAS2) Inhibits Zika Virus Replication through Activation of Type Ι IFN Signaling Pathway

Abstract

Background: 2′, 5′-oligoadenylate synthetase 2 (OAS2) has been known as an antiviral interferon-stimulated gene (ISG). However, the role of OAS2 on Zika virus (ZIKV) replication is still unknown. In this study, we sought to explore the effect of OAS2 on ZIKV replication and its underlying mechanism. Methods: We performed RNA-Seq in A549 cells with or without ZIKV infection. OAS2 or RIG-I was overexpressed by plasmid transfection or knocked down by siRNA in A549 cells. Expression levels of mRNA and protein of selected genes were detected by RT-qPCR and Western Blot, respectively. Interferon stimulated response element (ISRE) activity was examined by dual luciferase assay. Results: We found that ZIKV infection induced OAS2 expression through a RIG-I-dependent pathway. OAS2 overexpression inhibited ZIKV replication, while OAS2 knockdown increased ZIKV replication. We observed that OAS2 inhibited ZIKV replication through enhanced IFNβ expression, leading to the activation of the Jak/STAT signaling pathway. Conclusion: ZIKV infection induced OAS2 expression, which in turn exerted its anti-ZIKV activities through the IFN-activated Jak/STAT signaling pathway.

All About the RNA: Interferon-Stimulated Genes That Interfere With Viral RNA Processes

“…In fact, OAS1 and OAS2 are responsible for some antiviral activity against WNV and SINV, albeit to a lesser extent than OAS3/RNase L ( 67 ). OAS2 was found to inhibit the (+) ssRNA virus Zika virus (ZIKV) replication through positive regulation of IFN signaling ( 86 ). OAS2 may also play a role in lactation, as it was identified in a screen for genes with roles in mammary development ( 87 ).…”

COVID-19 severity in obese patients: Potential mechanisms and molecular targets for clinical intervention

“…Viral-PAMPs such as the DNA or RNA can trigger IFN production, which activate signaling cascade for lodging antiviral protein response in an autocrine or paracrine manner [ 21 ]. Type I, II, and III interferons differentially regulate the immune response through Janus associated kinases (JAK) and STAT pathway eventually stimulating the interferon stimulated genes (ISGs) [ 21 ], concerned with antiviral response protein such as 2′5′ oligoadenylate synthetase [ 22 ].…”

RIG-I Plays a Dominant Role in the Induction of Transcriptional Changes in Zika Virus-Infected Cells, which Protect from Virus-Induced Cell Death

“…Deficiency of PRRs increases ZIKV replication in human skin fibroblasts and mice lacking the type I IFN receptor (IFNAR), STAT2, MAVS or a combination of IRF transcription factors show higher viral replication and pathology [ 5 , 7 , 8 , 10 , 11 , 12 ]. ZIKV induces type I IFNs, and this is mainly dependent on MAVS, suggesting an important role of RIG-I and/or MDA5 in virus detection [ 7 , 13 , 14 , 15 , 16 , 17 , 18 ]. ZIKV antagonizes IFNAR signaling as viral replication is blocked only moderately if type I IFN is applied with or after ZIKV infection [ 19 ].…”