Characterization the regulation of herpesvirus miRNAs from the view of human protein interaction network

We performed topological analysis to explore the targeting propensities of herpesvirus miRNAs from the view of human PIN and found that (1) herpesvirus miRNAs significantly target more hubs, moreover, compared with non-hubs (non-bottlenecks), hubs (bottlenecks) are targeted by much more virus miRNAs and virus types. (2) There are significant differences in the degree and betweenness centrality between common and specific targets, specifically we observed a significant positive correlation between virus types targeting these nodes and the proportion of hubs, and (3) K-core and ER analysis determined that common targets are closer to the global PIN center. Compared with random conditions, the giant connected component (GCC) and the density of the sub-network formed by common targets have significantly higher values, indicating the module characteristic of these targets.Herpesvirus miRNAs preferentially target hubs and bottlenecks. There are significant differences between common and specific targets. Moreover, common targets are more intensely connected and occupy the central part of the network. These results will help unravel the complex mechanism of herpesvirus-host interactions and may provide insight into the development of novel anti-herpesvirus drugs.Herpesviruses are members of Herpesviridae family, a large family of DNA viruses that cause chronic, latent and recurrent infections in animals and humans. Herpesviruses are double-stranded DNA viruses with large genomes encoding complex virus particles and enzymes involved in a variety of cellular process, including nucleic acid metabolism, DNA synthesis, and protein processing [1]. In addition to herpesvirus proteins associated with pathogenic processes, herpesvirus-encoded microRNAs (miRNAs) have been also shown to play an indispensable role in herpesvirus pathogenesis [2]. miRNAs are a class of endogenous, single strand RNAs, approximately 22 nucleotides long that bind to 3'untranslated regions of transcript ca