VirHostNet: a knowledge base for the management and the analysis of proteome-wide virus–host interaction networks

Navratil, Vincent; de Chassey, Benoît; Meyniel, Laurène; Delmotte, Stéphane; Gautier, Christian; André, Patrice; Lotteau, Vincent; Rabourdin-Combe, Chantal

VirHostNet provides now a public access to the largest known resource of integrated virus-virus, virus-host and host-host protein interaction networks. Literature-and database-curated interactions have led to the definition of an original and high-confidence protein-protein interactions dataset. We have briefly illustrated the need of this high-confidence dataset for the characterization of cellular functions targeted by viruses. This resource may also be crucial for network-based analysis of molecular mechanisms involved during viral infections, such as cellular network properties disturbed after the connection of viral proteins. VirHostNet will also provide a backbone for automatic screening of specific protein domains or peptides motifs associated to virus-host interactions and hence may help to delineate at the proteome-wide scale footprints in both viral and host proteins sequences. VirHostNet will allow systematic prediction of virushost protein-protein interologs based on sequence homology criteria between closely related viral proteins. The knowledge-based system is also intended to integrate virus-host protein-protein interactions data derived by our team from high-throughput yeast-two hybrids experiments (Orthomyxovirus, Paramyxovirus, Flavivirus . . .). Thus, the availability of virus-virus and virus-host networks for a broad range of viruses will encourage comparative analysis and will be very helpful for the identification of molecular interactions associated to viral pathogenesis or virulence. As virus-host and virusvirus protein-protein interactions curation is one of the central features of the VirHostNet knowledge base, one of our missions is to keep these data up to date Users can select one or more proteins from the list of proteins (by default, all proteins are selected). Then, from the preferences panel, they have to choose the kind of interaction to retrieve (virus-virus, virus-host or host-host) or the database origin. Finally, they have to choose an operation ('neighbours' or 'sub-graph'). The 'neighbours' button allows users to retrieve all direct protein-protein interactions from a single protein or a list of selected proteins. The 'sub-graph' button allows users to retrieve only protein-protein interactions occurring between selected proteins (see result in Figure 4D ). (D) List of the 89 protein-protein interactions occurring between proteins of the mTOR pathway. For the interacting proteins, NCBI taxonomy name, ENSEMBL gene acc (host)-NCBI protein acc (viruses) and official gene name (host)-product name (viruses) are given. The '?' link at the end of each interaction line allows users to access interaction annotations ( Figure 4E ). In the protein-protein interactions research panel, in addition to 'neighbours' and 'sub-graph' buttons, the 'visualize' button allows from a list of interactions the graphical visualization of the resulting network (see result in Figure 5 ). (E) More detailed information concerning protein-protein interactions are available. PMID, PSI-MI method accession number and database origin of the selected interaction are given.