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.