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A comprehensive map of the influenza A virus replication cycle

Yukiko Matsuoka12, Hiromi Matsumae3, Manami Katoh1, Amie J Eisfeld4, Gabriele Neumann4, Takeshi Hase2, Samik Ghosh2, Jason E Shoemaker1, Tiago JS Lopes1, Tokiko Watanabe1, Shinji Watanabe15, Satoshi Fukuyama1, Hiroaki Kitano1267 and Yoshihiro Kawaoka110489*

Author Affiliations

1 JST ERATO Kawaoka infection-induced host responses project, Minato-ku, Tokyo 108-8639, Japan

2 The Systems Biology Institute, Minato-ku, Tokyo 108-0071, Japan

3 Department of Bioinformatics, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8540, Japan

4 Department of Pathological Science, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53711, USA

5 Laboratory of Veterinary Microbiology, Department of Veterinary Sciences, University of Miyazaki, Miyazaki 889-2192, Japan

6 Sony Computer Science Laboratories, Inc., Shinagawa, Tokyo 141-0022, Japan

7 Okinawa Institute of Science and Technology Graduate University, Onna-son, Okinawa 904-0495, Japan

8 Division of Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan

9 Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan

10 Laboratory of Bioresponses Regulation, Department of Biological Responses, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan

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BMC Systems Biology 2013, 7:97  doi:10.1186/1752-0509-7-97

Published: 2 October 2013



Influenza 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.


We 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.


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. Publicly available webtools will allow continuous updating to ensure the most reliable representation of the host-virus interaction network. The FluMap is available at webcite.

Drug targets; FluMap; Host factors; Influenza virus; Pathways