a Hubei Key Laboratory of Agricultural Bioinformatics, College of Informatics , Huazhong Agricultural University , Wuhan , People's Republic of China.
b Gongqing Institute of Science and Technology , Gongqing , People's Republic of China.
J Biomol Struct Dyn. 2019 Jun;37(9):2310-2321. doi: 10.1080/07391102.2018.1479659. Epub 2018 Nov 17.
In recent years, West Nile virus (WNV) has posed a great threat to global human health due to its explosive spread. Studying the protein-protein interactions (PPIs) between WNV and human is beneficial for understanding the pathogenesis of WNV and the immune response mechanism of human against WNV infection at the molecular level. In this study, we identified the human target proteins which interact with WNV based on protein structure similarity, and then the interacting pairs were filtered by the subcellular co-localization information. As a result, a network of 3346 interactions was constructed, involving 6 WNV proteins and 1970 human target proteins. To our knowledge, this is the first predicted interactome for WNV-human. By analyzing the topological properties and evolutionary rates of the human target proteins, it was demonstrated that these proteins tend to be the hub and bottleneck proteins in the human PPI network and are more conserved than the non-target ones. Triplet analysis showed that the target proteins are adjacent to each other in the human PPI network, suggesting that these proteins may have similar biological functions. Further, the functional enrichment analysis indicated that the target proteins are mainly involved in virus process, transcription regulation, cell adhesion, and so on. In addition, the common and specific targets were identified and compared based on the networks between WNV-human and Dengue virus II (DENV2)-human. Finally, by combining topological features and existing drug target information, we identified 30 potential anti-WNV human targets, among which 11 ones were reported to be associated with WNV infection. Communicated by Ramaswamy H. Sarma.
近年来，西尼罗河病毒（WNV）的爆发式传播对全球人类健康构成了巨大威胁。研究 WNV 与人之间的蛋白质-蛋白质相互作用（PPIs）有助于从分子水平上了解 WNV 的发病机制和人类对 WNV 感染的免疫反应机制。在本研究中，我们基于蛋白质结构相似性鉴定了与 WNV 相互作用的人类靶蛋白，然后根据亚细胞共定位信息筛选相互作用对。结果构建了一个包含 6 个 WNV 蛋白和 1970 个人类靶蛋白的 3346 个相互作用网络。据我们所知，这是 WNV-人类的第一个预测互作组。通过分析人类靶蛋白的拓扑性质和进化率，表明这些蛋白质在人类 PPI 网络中倾向于成为枢纽和瓶颈蛋白，并且比非靶蛋白更保守。三聚体分析表明，靶蛋白在人类 PPI 网络中彼此相邻，表明这些蛋白质可能具有相似的生物学功能。此外，功能富集分析表明，靶蛋白主要参与病毒过程、转录调控、细胞黏附等。此外，基于 WNV-人类和登革热病毒 II（DENV2）-人类之间的网络，鉴定并比较了共同和特异的靶蛋白。最后，通过结合拓扑特征和现有的药物靶标信息，我们鉴定了 30 个潜在的抗 WNV 人类靶标，其中 11 个被报道与 WNV 感染有关。Ramaswamy H. Sarma 通讯。
