Figure 1. Intraviral protein interactions in HSV-1.

(A) Phylogeny of the five investigated herpesviruses and their classification into the three subfamilies α, β, and γ. A timeline is added to indicate approximately when the different subfamilies were separated based on findings by McGeoch and colleagues [6],[7]. (B) Intraviral protein-protein interaction network for HSV-1. The proteins are coloured according to their conservation in the herpesvirus phylogeny: the blue nodes are core proteins conserved in all five viruses, two nodes (pink) are conserved in α and γ herpesviruses, several red ones in α herpesviruses and the grey ones are specific to HSV-1. Edges indicate observed interactions in HSV-1, and red edges indicate previously reported interactions. The protein interaction network was generated using the Cytoscape software (www.cytoscape.org) [58].. (C) node degree distribution on a linear or logarithmic (inset) scale. The herpesviral networks can be approximated by power law distributions (Table S3). (D) Simulations of deliberate attack on HSV-1 in comparison to two human networks by removing their most highly connected nodes in decreasing order. After each node is removed, the new network characteristic path length (average distance between any two nodes) of the remaining network is plotted as a multiple or fraction of the original parameters. The herpesviral networks consistently exhibited a higher attack tolerance, as the increase in path length is considerably smaller.