Figure 1 Human host-flavivirus Ipatasertib protein-protein interaction network. The flavivirus NS3 and NS5 protein interactome, resulting from our Y2H screen and the literature curation, is represented here graphically. Red nodes denote viral proteins; blue nodes denotes human proteins identified by our screen; black nodes are human proteins identified in the literature; gray nodes are human proteins identified both in our screen and in the literature; red edges denote interaction between human and check details viral proteins; blue edges denote interaction between human proteins. Human proteins interacting with both viral proteins or with other human
proteins are positioned centrally. Table 2 Analysis of the human host-flavivirus protein-protein interaction network Nb of targeting viruses Nb of targeted human proteins Targeted human proteins 4 2 (1.7%) APBB1IP, ENO1 3 10 (8.3%) ARID2, AZI2, CAMTA2, CEP63, MLPH, MYH9, NME3, TAF15, TRAF4, VPS11 2 26 buy Necrostatin-1 (21.7%) ARNTL, BCL2L14, CCDC99, CEP250, DNTTIP2, FAM184A, GGA1, GRN, JAG1, LAMB2, NFKBIA, OPTN, PABPC1, PDE4DIP, PHC2, PHLDB3, PIAS3, RNF125, RNUXA, SCRIB, SNRPA, TOM1L1, TRIM21, TXNDC9, VIM, ZBTB17 1 82 (68.3%) – We determined
the number of flavivirus species that interact with each cellular host protein found to be targeted by NS3 or NS5 (Y2H plus literature). To further describe the topological properties of the flavivirus interaction network in relation to the whole human interactome, we then took advantage of the VirHostNet knowledgebase which includes an extensive assembly of human-human and viral-human interactions . We thus calculated the local (degree) and global Thiamet G (betweenness) centrality measures of the human proteins targeted by NS3, NS5 or both flavivirus proteins integrated into the human interactome (Table 3). Briefly, the degree of a protein in a network refers to its number of direct partners and is therefore a measure of local centrality.
Betweenness is a global measure of centrality, as it measures the number of shortest paths (the minimum distance between two proteins in the network) that cross a given protein. The 120 identified human proteins interacting with NS3 and NS5 were shown to have a higher average degree i.e. local connectivity (22, 93 versus 10, 43) and betweenness i.e. global centrality (4, 02.10-4 versus 1, 30.10-4) in comparison with the human proteins belonging to the human interactome (Table 3). In addition, the degree and the betweenness distributions of human proteins interacting with NS3 and NS5 are significantly distinct from the proteins belonging to the human interactome distributions (U-test, all p-values < 10-12, additional file 6).