A dual controllability analysis of influenza virus-host protein-protein interaction networks for antiviral drug target discovery

Ackerman, Emily E.; Alcorn, John F.; Hase, Takeshi; Shoemaker, Jason E.

A network representation of the cellular environment demonstrates that the effects of infection (represented by the addition of virus-host interactions) cascade through the system, demonstrated by the alteration of basic topology measures. The betweenness shift between the two networks, particularly in IAV interacting proteins, supplies evidence that the topological effect of viral infection is wide reaching (Tables 1 and 4) . Further, a comparison of driver protein betweenness for those that are also IAV interacting proteins in comparison to those that are not shows a significant difference. Driver proteins that are IAV interacting are not receiving control influence from viral proteins (dictated by the maximum matching requirement that each protein only control a single protein) and require additional external influence to achieve network control. However, the increased betweenness of proteins that are both driver and IAV interacting proteins suggests that this group is still of great importance to information flow through the network. This is one example where differences in network topology measures can emphasize the importance of select proteins that are overlooked by controllability principles.