The 2′,5′-oligoadenylate synthetase 1b is a potent inhibitor of West Nile virus replication inside infected cells
The 2′,5′-oligoadenylate synthetase 1b is a potent inhibitor of West Nile virus replication inside infected cells
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DOI：
10.1074/jbc.m508649200
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发表时间：
2006-02-24
影响因子：
4.8
通讯作者：
Desprès, P
中科院分区：
文献类型：
--
作者：
Kajaste-Rudnitski, A;Mashimo, T;Desprès, P
与核糖核酸内切酶RNase L相关的2 '，5'-寡腺苷酸合成酶（OAS）蛋白是干扰素调节的OAS/RNase L系统的组分，该系统是已知在先天性抗病毒免疫中起重要作用的RNA衰变途径。大量的证据表明，小鼠Oas基因的1b亚型（Oas 1b）在体内抵抗西尼罗河病毒（WNV）感染中起着关键作用。西尼罗河病毒是一种阳性单链RNA病毒，可引起大范围动物和人类的严重脑炎。为了研究WNV对Oas 1b抗病毒途径敏感性的分子基础，我们建立了一个稳定的小鼠成纤维细胞克隆，该细胞克隆在Tet-Off表达系统的控制下上调Oas 1b蛋白表达。我们发现，鼠细胞响应Oas 1b表达有效抑制西尼罗河病毒复制。Oas 1b的抗病毒作用基本上局限于病毒生命周期的早期阶段。我们发现西尼罗河病毒不能有效感染Oas 1b表达细胞是由于正链病毒RNA水平的急剧下降。因此，Oas 1b代表了一种抗病毒途径，通过防止病毒RNA在感染细胞内积累，对WNV复制发挥抑制作用。
The 2',5'-oligoadenylate synthetase (OAS) proteins associated with endoribonuclease RNase L are components of the interferon-regulated OAS/RNase L system, which is an RNA decay pathway known to play an important role in the innate antiviral immunity. A large body of evidence suggests a critical role for the 1b isoform of the mouse Oas gene (Oas1b) in resistance to West Nile virus (WNV) infection in vivo. WNV is a positive, single-stranded RNA virus responsible for severe encephalitis in a large range of animal species and humans. To investigate the molecular basis for the sensitivity of WNV to the Oas1b antiviral pathway, we established a stable mouse fibroblastic cell clone that up-regulates Oas1b protein expression under the control of the Tet-Off expression system. We showed that murine cells respond to Oas1b expression by efficiently inhibiting WNV replication. The antiviral action of Oas1b was essentially restricted to the early stages in virus life cycle. We found that the inability of WNV to productively infect the Oas1b-expressing cells was attributable to a dramatic reduction in positive-stranded viral RNA level. Thus, Oas1b represents an antiviral pathway that exerts its inhibitory effect on WNV replication by preventing viral RNA accumulation inside infected cells.