Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu, China.
Liver Center and Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Viruses. 2020 Apr 8;12(4):418. doi: 10.3390/v12040418.
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.
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.
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.
ZIKV infection induced OAS2 expression, which in turn exerted its anti-ZIKV activities through the IFN-activated Jak/STAT signaling pathway.
2',5'-寡聚腺苷酸合成酶 2（OAS2）是一种抗病毒干扰素刺激基因（ISG）。然而，OAS2 对寨卡病毒（ZIKV）复制的作用尚不清楚。在本研究中，我们试图探讨 OAS2 对 ZIKV 复制的影响及其潜在机制。
我们在 A549 细胞中进行了 RNA-Seq 实验，分别观察有无 ZIKV 感染。通过质粒转染或 siRNA 敲低在 A549 细胞中过表达 OAS2 或 RIG-I。通过 RT-qPCR 和 Western Blot 分别检测选定基因的 mRNA 和蛋白表达水平。通过双荧光素酶报告基因检测干扰素刺激反应元件（ISRE）活性。
我们发现 ZIKV 感染通过 RIG-I 依赖性途径诱导 OAS2 表达。OAS2 过表达抑制 ZIKV 复制，而 OAS2 敲低则增加 ZIKV 复制。我们观察到 OAS2 通过增强 IFNβ 的表达抑制 ZIKV 复制，从而激活 Jak/STAT 信号通路。
ZIKV 感染诱导 OAS2 表达，OAS2 进而通过 IFN 激活的 Jak/STAT 信号通路发挥其抗 ZIKV 活性。
