Functional dissection of virus-human crosstalk mediated by miRNAs based on the VmiReg database

Recently, a number of viruses have been shown to encode microRNAs (miRNAs), and they play important roles in several biological processes, enhancing the intricacies of the virus-host crosstalk. However, systematically deciphering the characteristics of crosstalk mediated by viral and human miRNAs has been hampered by the lack of high-confidence targets. Here, a user-friendly platform is developed to provide experimentally validated and predicted target genes of viral miRNAs as well as their functions, named VmiReg. To explore the virus-human crosstalk meditated by miRNAs, validated human cellular targets of viral and cellular miRNAs are analyzed. As a result, target genes of viral miRNAs are prone to be silenced by human miRNAs. Two kinds of targets have globally significantly high functional similarities and are more often found simultaneously in many important biological functions, even in disease genes, particularly cancer genes, and essential genes. In addition, viral and human miRNA targets are in close proximity within the protein-protein interaction network, indicating frequent communication via physical interactions to participate in the same functions. Finally, multiple dense modules intuitively exhibit crosstalk between viral and cellular miRNAs. Furthermore, most co-regulated genes tend to be in important locations of modules. The lymphoma-related module is one of the typical examples. Our study suggests that the functional importance of cellular genes targeted by viral miRNAs and the intricate virus-host crosstalk mediated by miRNAs may be performed via the sharing of target genes or physical interactions, providing a new direction in further researching the roles of miRNAs in infection.