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bioRxiv · 10.1101/429712

A Dual Controllability Analysis of Influenza Virus-Host Protein-Protein Interaction Networks for Antiviral Drug Target Discovery

Ackerman, E. E.·Alcorn, J. F.·Hase, T.·Shoemaker, J. E.
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Abstract

Host factors of influenza virus replication are often found in key topological positions within protein-protein interaction networks. This work explores how protein states can be manipulated through controllability analysis: the determination of the minimum manipulation needed to drive the cell system to any desired state. Here, we complete a two-part controllability analysis of two protein networks: a host network representing the healthy cell state and an influenza A virus-host network representing the infected cell state. This knowledge can be utilized to understand disease dynamics and isolate proteins for study as drug target candidates. Both topological and controllability analyses provide evidence of wide-reaching network effects stemming from the addition of viral-host protein interactions. Virus interacting and driver host proteins are significant both topologically and in controllability, therefore playing important roles in cell behavior during infection. 24 proteins are identified as holding regulatory roles specific to the infected cell by measures of topology, controllability, and functional role. These proteins are recommended for further study as potential antiviral drug targets.\n\nImportanceSeasonal outbreaks of influenza A virus are a major cause of illness and death around the world each year, with a constant threat of pandemic infection. Even so, the FDA has only approved four treatments, two of which are unsuited for at risk groups such as children and those with breathing complications. This research aims to increase the efficiency of antiviral drug target discovery using existing protein-protein interaction data and network analysis methods. Controllability analyses identify key regulating host factors of the infected cells progression, findings which are supported by biological context. These results are beneficial to future studies of influenza virus, both experimental and computational.

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Ackerman, E. E., Alcorn, J. F., Hase, T., Shoemaker, J. E.. 2018-09-27. A Dual Controllability Analysis of Influenza Virus-Host Protein-Protein Interaction Networks for Antiviral Drug Target Discovery. https://doi.org/10.1101/429712

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