Rachita H R, Nagarajaram H A
Centre for DNA Fingerprinting and Diagnostics, Gruhakalpa, 5-4-399/B, Nampally, Hyderabad 500001, India.
Mol Biosyst. 2014 Jul 29;10(9):2448-58. doi: 10.1039/c4mb00219a.
Viruses, despite having small genomes and few proteins, make an array of interactions with host proteins as they solely depend on host machinery for their replication and reproduction. Hence, analysis of the Human-Virus Protein-Protein Interaction Network (Hu-Vir PPI network) helps us to gain certain insights into the molecular mechanisms underlying the hijacking of host cell machinery by viruses for their perpetuation. Here we report an analysis of the Human-Virus Bridged PPI Networks that has led us to identify viral articulation points (VAPs) which connect unconnected components of the Human-PPI (Hu-PPI) network. VAPs cross-link peripheral nodes to the giant component of the Hu-PPI network. VAPs interact with a number of relatively lower topologically central human proteins and are conserved among related viruses. The linked nodes comprise of those that are mostly expressed during viral infection, as well as those that are found exclusively in some metabolic pathways, indicating that the novel viral mediation of certain human protein-protein interactions may form the basis for virus-specific tuning of the host machinery. The functional importance of VAPs and their interaction partners in virus replication make them potential drug targets against viral infection. Our investigations also led to the discovery of an example of a Human Endogenous Retrovirus (HERV) encoded protein, syncytin, as an Articulation Point (AP) in the Hu-PPI network, suggesting that VAPs may be retained in a genome if they result in any beneficial function in the host.
病毒尽管基因组小且蛋白质数量少，但由于其复制和繁殖完全依赖宿主机制，所以会与宿主蛋白质产生一系列相互作用。因此，对人类-病毒蛋白质-蛋白质相互作用网络（Hu-Vir PPI网络）的分析有助于我们深入了解病毒劫持宿主细胞机制以实现自身延续的分子机制。在此，我们报告了对人类-病毒桥接PPI网络的分析，该分析使我们识别出了病毒连接点（VAPs），这些连接点连接了人类PPI（Hu-PPI）网络中未连接的组件。VAPs将外围节点交联到Hu-PPI网络的巨大组件上。VAPs与许多拓扑中心性相对较低的人类蛋白质相互作用，并且在相关病毒中保守。相连的节点包括那些在病毒感染期间大多表达的节点，以及那些仅在某些代谢途径中发现的节点，这表明某些人类蛋白质-蛋白质相互作用的新型病毒介导可能构成病毒对宿主机制进行特异性调节的基础。VAPs及其相互作用伙伴在病毒复制中的功能重要性使其成为抗病毒感染的潜在药物靶点。我们的研究还发现了人类内源性逆转录病毒（HERV）编码的一种蛋白质——合胞素，它是Hu-PPI网络中的一个连接点（AP），这表明如果VAPs在宿主中产生任何有益功能，它们可能会保留在基因组中。
