Beijing Institute of Radiation Medicine, Beijing 100850, China.
Bioinformatics. 2013 Oct 1;29(19):2375-9. doi: 10.1093/bioinformatics/btt391. Epub 2013 Aug 7.
Human miRNAs have recently been found to have important roles in viral replication. Understanding the patterns and details of human miRNA interactions during virus-host interactions may help uncover novel antiviral therapies. Based on the abundance of knowledge available regarding protein-protein interactions (PPI), virus-host protein interactions, experimentally validated human miRNA-target pairs and transcriptional regulation of human miRNAs, it is possible to explore the complex regulatory network that exists between viral proteins and human miRNAs at the system level.
By integrating current data regarding the virus-human interactome and human miRNA-target pairs, the overlap between targets of viral proteins and human miRNAs was identified and found to represent topologically important proteins (e.g. hubs or bottlenecks) at the global center of the human PPI network. Viral proteins and human miRNAs were also found to significantly target human PPI pairs. Furthermore, an overlap analysis of virus targets and transcription factors (TFs) of human miRNAs revealed that viral proteins preferentially target human miRNA TFs, representing a new pattern of virus-host interactions. Potential feedback loops formed by viruses, human miRNAs and miRNA TFs were also identified, and these may be exploited by viruses resulting in greater virulence and more effective replication strategies.
人类 microRNA 最近被发现在病毒复制中具有重要作用。了解病毒-宿主相互作用过程中人类 microRNA 相互作用的模式和细节，可能有助于发现新的抗病毒疗法。基于现有关于蛋白质-蛋白质相互作用（PPI）、病毒-宿主蛋白相互作用、经实验验证的人类 microRNA-靶对以及人类 microRNA 转录调控的丰富知识，有可能在系统水平上探索病毒蛋白和人类 microRNA 之间存在的复杂调控网络。
通过整合当前关于病毒-人类相互作用组和人类 microRNA-靶对的数据，确定了病毒蛋白和人类 microRNA 的靶标重叠，并发现其代表了人类 PPI 网络全局中心的拓扑重要蛋白（例如，枢纽或瓶颈）。还发现病毒蛋白和人类 microRNA 显著靶向人类 PPI 对。此外，对病毒靶标和人类 microRNA 的转录因子（TFs）的重叠分析表明，病毒蛋白优先靶向人类 microRNA TFs，这代表了一种新的病毒-宿主相互作用模式。还鉴定了由病毒、人类 microRNA 和 microRNA TFs 形成的潜在反馈回路，这些回路可能被病毒利用，从而导致更高的毒力和更有效的复制策略。
