Comprehensive characterization of human-virus protein-protein interactions reveals disease comorbidities and potential antiviral drugs

The protein-protein interactions (PPIs) between human and viruses play important roles in viral infection and host immune responses. Rapid accumulation of experimentally validated human-virus PPIs provides an unprecedented opportunity to investigate the regulatory pattern of viral infection. However, we are still lack of knowledge about the regulatory patterns of human-virus interactions. We collected 27,293 experimentally validated human-virus PPIs, covering 8 virus families, 140 viral proteins and 6059 human proteins. Functional enrichment analysis revealed that the viral interacting proteins were likely to be enriched in cell cycle and immune-related pathways. Moreover, we analysed the topological features of the viral interacting proteins and found that they were likely to locate in central regions of human PPI network. Based on network proximity analyses of diseases genes and human-virus interactions in the human interactome, we revealed the associations between complex diseases and viral infections. Network analysis also implicated potential antiviral drugs that were further validated by text mining. Finally, we presented the Human-Virus Protein-Protein Interaction database (HVPPI, http://bio-bigdata.hrbmu.edu.cn/HVPPI), that provides experimentally validated human-virus PPIs as well as seamlessly integrates online functional analysis tools. In summary, comprehensive understanding the regulatory pattern of human-virus interactome will provide novel insights into fundamental infectious mechanism discovery and new antiviral therapy development.