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.

An analysis of both protein sets of interest was performed using Ingenuity Pathway Analysis (IPA) [48] . The network created for the robust protein set identified cellular compromise, cell death, and cell cycle functions. The network created for the global protein set identified protein synthesis functions, all centered around NF-kB. The global network notably recognizes six proteins . Four proteins in the robust network (CELF1, SF384, SRPK2, and HNRNPA0, the last of which appears in both protein sets) were identified for their involvement in mRNA processing (p-value: 3.33 × 10 − 6 ). Lastly, Interferome v2.01 [49] was used to determine if the 11 robust proteins and 24 global proteins are interferon regulated genes (IRGs). All 11 robust proteins are identified as IRGs and exhibit a 2-fold change in expression when treated with interferon in at least one experimental dataset. 20 of 24 global proteins are identified as IRGs and exhibit a 2-fold change in expression in at least one experimental dataset. 6 global proteins are identified in more than 10 studies. In particular, HNRNPA0 and PPA1 are significantly down regulated in 20 and 63 datasets, respectively. These results point toward the involvement of the predicted protein subsets in immune response events.