Drexel Institute for Biotechnology and Virology Research, Department of Microbiology and Immunology, Drexel University College of Medicine, Doylestown, Pennsylvania 18902, USA.
J Virol. 2010 Aug;84(16):8332-41. doi: 10.1128/JVI.02199-09. Epub 2010 Jun 9.
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.
干扰素 (IFNs) 是宿主先天抗病毒免疫反应的关键介质。为了鉴定引发针对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]）的抗病毒状态的 IFN 刺激基因 (ISGs)，我们测试了 36 种通常由 IFN-α诱导的 ISGs，以评估它们对两种病毒的抗病毒活性。我们发现，当这五种 ISGs 分别在 HEK293 细胞中表达时，它们能够有效地抑制 WNV 和/或 DENV 感染。机制分析表明，两种结构相关的细胞膜蛋白，IFITM2 和 IFITM3，破坏了病毒感染的早期步骤（进入和/或脱壳）。相比之下，三种 IFN 诱导的细胞酶， viperin、ISG20 和双链 RNA 激活的蛋白激酶，抑制了病毒蛋白和/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 ISGs 共同介导的，这些 ISGs 破坏了 DENV 和 WNV 生命周期的多个步骤。
