Identification of Five Interferon-Induced Cellular Proteins That Inhibit West Nile Virus and Dengue Virus Infections
Identification of Five Interferon-Induced Cellular Proteins That Inhibit West Nile Virus and Dengue Virus Infections
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DOI：
10.1128/jvi.02199-09
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发表时间：
2010-08-15
影响因子：
5.4
通讯作者：
Guo, Ju-Tao
中科院分区：
文献类型：
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作者：
Jiang, Dong;Weidner, Jessica M.;Guo, Ju-Tao
干扰素（IFN）是宿主先天性抗病毒免疫应答的关键介质。为了鉴定IFN刺激的基因（ISG），激发抗两种医学上重要的黄病毒，西尼罗河病毒（WNV）和登革热病毒（DENV）的抗病毒状态，我们测试了36个ISG，通常由IFN-α诱导的抗病毒活性。我们发现，当它们在HEK 293细胞中单独表达时，五个ISG有效地抑制WNV和/或DENV感染。机制分析表明，两个结构相关的细胞质膜蛋白，IFITM 2和IFITM 3，破坏病毒感染的早期步骤（进入和/或脱壳）。相反，三种IFN诱导的细胞酶，蝰蛇蛋白，ISG 20和双链RNA激活的蛋白激酶，抑制病毒蛋白和/或RNA生物合成的步骤。因此，我们的研究结果表明，IFN-α的抗病毒活性是由一组ISG共同介导的，这些ISG破坏了DENV和WNV生命周期的多个步骤。
Interferons (IFNs) are key mediators of the host innate antiviral immune response. To identify IFN-stimulated genes (ISGs) that instigate an antiviral state against two medically important flaviviruses, West Nile virus (WNV) and dengue virus (DENV), we tested 36 ISGs that are commonly induced by IFN-alpha for antiviral activity against the two viruses. We discovered that five ISGs efficiently suppressed WNV and/or DENV infection when they were individually expressed in HEK293 cells. Mechanistic analyses revealed that two structurally related cell plasma membrane proteins, IFITM2 and IFITM3, disrupted early steps (entry and/or uncoating) of the viral infection. In contrast, three IFN-induced cellular enzymes, viperin, ISG20, and double-stranded-RNA-activated protein kinase, inhibited steps in viral proteins and/or RNA biosynthesis. Our results thus imply that the antiviral activity of IFN-alpha is collectively mediated by a panel of ISGs that disrupt multiple steps of the DENV and WNV life cycles.