A comprehensive map of the influenza A virus replication cycle

Manami Katoh,Amie J Eisfeld,Hiroaki Kitano,Shinji Watanabe,Tokiko Watanabe,Hiromi Matsumae,Samik Ghosh,Yukiko Matsuoka,Satoshi Fukuyama,Tiago JS Lopes,Jason E Shoemaker,Yoshihiro Kawaoka,Gabriele Neumann,Takeshi Hase

doi:10.1186/1752-0509-7-97

Abstract

BackgroundInfluenza is a common infectious disease caused by influenza viruses. Annual epidemics cause severe illnesses, deaths, and economic loss around the world. To better defend against influenza viral infection, it is essential to understand its mechanisms and associated host responses. Many studies have been conducted to elucidate these mechanisms, however, the overall picture remains incompletely understood. A systematic understanding of influenza viral infection in host cells is needed to facilitate the identification of influential host response mechanisms and potential drug targets.DescriptionWe constructed a comprehensive map of the influenza A virus (‘IAV’) life cycle (‘FluMap’) by undertaking a literature-based, manual curation approach. Based on information obtained from publicly available pathway databases, updated with literature-based information and input from expert virologists and immunologists, FluMap is currently composed of 960 factors (i.e., proteins, mRNAs etc.) and 456 reactions, and is annotated with ~500 papers and curation comments. In addition to detailing the type of molecular interactions, isolate/strain specific data are also available. The FluMap was built with the pathway editor CellDesigner in standard SBML (Systems Biology Markup Language) format and visualized as an SBGN (Systems Biology Graphical Notation) diagram. It is also available as a web service (online map) based on the iPathways+ system to enable community discussion by influenza researchers. We also demonstrate computational network analyses to identify targets using the FluMap.ConclusionThe FluMap is a comprehensive pathway map that can serve as a graphically presented knowledge-base and as a platform to analyze functional interactions between IAV and host factors. Publicly available webtools will allow continuous updating to ensure the most reliable representation of the host-virus interaction network. The FluMap is available at http://www.influenza-x.org/flumap/.

Highlights

Influenza is a common infectious disease caused by influenza viruses
By using standard formats, we have enabled FluMap to be adaptable to multiple network analysis tools such as Cytoscape or to simulation by employing user-supplied kinetic laws and Systems Biology Markup Language (SBML)-compliant simulators
The controllability analysis we applied here does not take into consideration the nature of the interaction, our analysis identified several events known to be critical for the influenza A virus (IAV) life cycle, suggesting that the algorithm [327] can be effectively applied to process-descriptive pathway networks such as FluMap to identify and prioritize factors that could be targeted to affect the IAV life cycle

Summary

Conclusion

The FluMap is a comprehensive pathway map that can serve as a graphically presented knowledge-base and as a platform to analyze functional interactions between IAV and host factors. Available webtools will allow continuous updating to ensure the most reliable representation of the host-virus interaction network.

Background

Findings

Conclusions

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