Structure-based prediction of West Nile virus-human protein–protein interactions

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（West Nile Virus, WNV）因其暴发式传播，对全球人类健康构成了严重威胁。解析西尼罗河病毒与人类的蛋白质-蛋白质相互作用（protein-protein interactions, PPIs），有助于从分子层面理解该病毒的致病机制，以及人类对抗病毒感染的免疫应答机制。本研究基于蛋白质结构相似性，筛选得到与西尼罗河病毒存在相互作用的人类靶蛋白，并通过亚细胞共定位信息对相互作用蛋白对进行过滤。最终构建得到包含3346条相互作用的病毒-人类蛋白互作网络，涉及6种西尼罗河病毒蛋白与1970种人类靶蛋白。据我们所知，这是首个针对西尼罗河病毒-人类互作组的预测数据集。通过对人类靶蛋白的拓扑属性与进化速率进行分析，本研究发现此类蛋白在人类蛋白质-蛋白质相互作用网络中更倾向于充当枢纽蛋白与瓶颈蛋白，且相较于非靶标蛋白更为保守。三元组分析结果显示，人类靶蛋白在人类蛋白质-蛋白质相互作用网络中彼此相邻，提示这类蛋白可能具有相似的生物学功能。进一步的功能富集分析表明，人类靶蛋白主要参与病毒生命周期进程、转录调控、细胞黏附等生物学过程。此外，本研究基于西尼罗河病毒-人类与登革病毒Ⅱ型（Dengue Virus 2, DENV2）-人类的互作网络，筛选得到共有的与特异性的人类靶蛋白，并对二者进行了比较分析。最后，本研究结合拓扑特征与现有药物靶标信息，筛选得到30个潜在的抗西尼罗河病毒人类靶标，其中11个已被报道与西尼罗河病毒感染相关。由Ramaswamy H. Sarma转交