Finding a needle in a haystack of needles - a productive hunt for interferon stimulated genes with antiviral activity.
Finding a needle in a haystack of needles - a productive hunt for interferon stimulated genes with antiviral activity.
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大海捞针——对具有抗病毒活性的干扰素刺激基因的有效搜寻。
DOI：
10.1038/icb.2013.108
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发表时间：
2014
影响因子：
4
通讯作者：
Kagan,JonathanC
中科院分区：
文献类型：
--
作者：
Franz,KateM;Kagan,JonathanC
病毒感染后，宿主模式识别受体启动信号级联，激活 I 型干扰素 (IFN) 的产生。 IFN 通过协调表达数百个称为干扰素刺激基因 (ISG) 的基因来保护细胞。许多 ISG 具有已知或提议的功能，但每种特定功能如何有助于病毒控制尚未确定。Schoggins 等人的研究通过调查单一 ISG 有效对抗的病毒谱进一步推进了这个问题。为此，作者利用了他们之前发布的基于慢病毒载体的筛选平台2。简而言之，用编码 ISG 的慢病毒转导细胞，并用编码 GFP 报告基因的重组病毒感染每个细胞系。通过流式细胞术监测病毒基因表达。作者使用该系统来测试单个 ISG 在感染过程中抑制或增强病毒基因表达的能力。总之，他们检查了 7 个病毒家族的 14 种病毒（包括 DNA 和 RNA）感染期间 ISG 表达的影响。通过这次筛选，47 个基因被鉴定为抑制病毒基因表达的基因，25 个基因被证明可以增强感染性。
Upon virus infection, host pattern recognition receptors initiate signaling cascades that activate the production of type-I interferon (IFN). IFNs protect cells through the coordinated expression of hundreds of genes termed interferon stimulated genes (ISGs). Many ISGs have known or proposed functions, but how each specific function contributes to viral control has not been determined.The study by Schoggins et al1 furthers this question by investigating the spectrum of viruses a singular ISG is effective against. To do so, the authors utilize their previously published lentiviral vector-based screening platform2. In short, cells are transduced with a lentivirus encoding an ISG and each cell line is infected with a recombinant virus encoding a GFP reporter gene. Viral gene expression is monitored by flow cytometry. The authors use this system to test the capacity of single ISGs to inhibit or enhance viral gene expression during infection. In all, they examined the effects of ISG expression during infection with 14 viruses, both DNA and RNA, spanning 7 virus families. From this screen, 47 genes were identified as inhibitory for viral gene expression and 25 genes were shown to enhance infectivity.