Université de Lyon, France, INSERM, U851, 21 Avenue Tony Garnier, Lyon, F-69007, France.
J Proteome Res. 2010 Jul 2;9(7):3527-36. doi: 10.1021/pr100326j.
Innate immunity has evolved complex molecular pathways to protect organisms from viral infections. One pivotal line of cellular defense is the induction of the antiviral effect of interferon. To circumvent this primary response and achieve their own replication, viruses have developed complex molecular strategies. Here, we provide a systems-level study of the human type I interferon system subversion by the viral proteome, by reconstructing the underlying protein-protein interaction network. At this network level, viruses establish a massive and a gradual attack, from receptors to transcription factors, by interacting preferentially with highly connected and central proteins as well as interferon-induced proteins. We also demonstrate that viruses significantly target 22% of the proteins directly interacting with the type I interferon system network, suggesting the relevance of our network-based method to identify new candidates involved in the regulation of the antiviral response. Finally, based on the comparative analysis of interactome profiles across four viral families, we provide evidence of common and differential targeting strategies.
先天免疫系统进化出了复杂的分子途径来保护生物免受病毒感染。细胞防御的一个关键防线是诱导干扰素的抗病毒作用。为了规避这种初始反应并实现自身复制，病毒已经发展出了复杂的分子策略。在这里，我们通过重建潜在的蛋白质-蛋白质相互作用网络，对病毒蛋白质组对 I 型干扰素系统的颠覆进行了系统水平的研究。在这个网络层面上，病毒通过与高度连接和中心的蛋白质以及干扰素诱导的蛋白质优先相互作用，从受体到转录因子，建立了大规模的、渐进的攻击。我们还证明，病毒显著靶向与 I 型干扰素系统网络直接相互作用的 22%的蛋白质，这表明我们基于网络的方法对于识别新的与抗病毒反应调控相关的候选物是有效的。最后，基于对四个病毒家族的互作组谱的比较分析，我们提供了共同和差异靶向策略的证据。
