Common Nodes of Virus-Host Interaction Revealed Through an Integrated Network Analysis
Common Nodes of Virus-Host Interaction Revealed Through an Integrated Network Analysis
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DOI：
10.3389/fimmu.2019.02186
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发表时间：
2019-10-04
影响因子：
7.3
通讯作者：
Kandasamy, Richard K.
中科院分区：
文献类型：
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作者：
Bosl, Korbinian;Ianevski, Aleksandr;Kandasamy, Richard K.
病毒是急性和慢性传染病的主要原因之一，因此是造成全球疾病负担的主要因素。几项研究表明，病毒是如何进化到劫持基本细胞途径，并通过调节关键宿主因子和信号通路来逃避先天免疫反应的。对这些多项研究的集体看法可能会促进我们对病毒-宿主相互作用的理解，并为病毒疾病的治疗提供新的治疗视角。在这里，我们进行了一项综合荟萃分析，以阐明17种不同的宿主-病毒相互作用。网络和生物信息学分析表明，基因组较小的病毒如何通过靶向具有高度无序区的多功能和高度连接的宿主蛋白来有效地实现最大效果。我们还确定了所有病毒攻击的核心细胞过程子网络。与功能RNA干扰(RNAi)数据集的整合表明，病毒复制需要很大比例的靶标。此外，我们进行了互动组信息的药物再利用筛选，并确定了广谱抗病毒药物对丙型肝炎病毒和人类偏肺病毒的新活性。总之，这些正交数据集可以作为假设生成和后续研究的平台，以拓宽我们对病毒逃避情况的理解。
Viruses are one of the major causes of acute and chronic infectious diseases and thus a major contributor to the global burden of disease. Several studies have shown how viruses have evolved to hijack basic cellular pathways and evade innate immune response by modulating key host factors and signaling pathways. A collective view of these multiple studies could advance our understanding of virus-host interactions and provide new therapeutic perspectives for the treatment of viral diseases. Here, we performed an integrative meta-analysis to elucidate the 17 different host-virus interactomes. Network and bioinformatics analyses showed how viruses with small genomes efficiently achieve the maximal effect by targeting multifunctional and highly connected host proteins with a high occurrence of disordered regions. We also identified the core cellular process subnetworks that are targeted by all the viruses. Integration with functional RNA interference (RNAi) datasets showed that a large proportion of the targets are required for viral replication. Furthermore, we performed an interactome-informed drug re-purposing screen and identified novel activities for broad-spectrum antiviral agents against hepatitis C virus and human metapneumovirus. Altogether, these orthogonal datasets could serve as a platform for hypothesis generation and follow-up studies to broaden our understanding of the viral evasion landscape.