title: F1Fo-ATPase, F-type proton-translocating ATPase, at the plasma membrane is critical for efficient influenza virus budding.
abstract: The identification of host factors involved in virus replication is important to understand virus life cycles better. Accordingly, we sought host factors that interact with the influenza viral nonstructural protein 2 by using coimmunoprecipitation followed by mass spectrometry. Among proteins associating with nonstructural protein 2, we focused on the β subunit of the F1Fo-ATPase, which received a high probability score in our mass spectrometry analysis. The siRNA-mediated down-regulation of the β subunit of the F1Fo-ATPase reduced influenza virion formation and virus growth in cell culture. We further found that efficient influenza virion formation requires the ATPase activity of F1Fo-ATPase and that plasma membrane-associated, but not mitochondrial, F1Fo-ATPase is important for influenza virion formation and budding. Hence, our data identify plasma membrane-associated F1Fo-ATPase as a critical host factor for efficient influenza virus replication.
authors.affiliation: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Gorai
authors.forename: Hideo
authors.initials: H
authors.lastname: Goto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Noda
authors.forename: Tokiko
authors.initials: T
authors.lastname: Watanabe
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kozuka-Hata
authors.forename: Masaaki
authors.initials: M
authors.lastname: Oyama
authors.forename: Ryo
authors.initials: R
authors.lastname: Takano
authors.forename: Gabriele
authors.initials: G
authors.lastname: Neumann
authors.forename: Shinji
authors.initials: S
authors.lastname: Watanabe
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawaoka
mesh_terms: D002462:Cell Membrane / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D007251:Influenza, Human / Q000821:virology; D013058:Mass Spectrometry / Q000379:methods; D008954:Models, Biological; D015233:Models, Statistical; D009975:Orthomyxoviridae / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D006180:Proton-Translocating ATPases / Q000737:chemistry* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000737:chemistry*; D057074:Virus Release; D014779:Virus Replication
chemical_list: D034741:RNA, Small Interfering; D017361:Viral Nonstructural Proteins; D006180:Proton-Translocating ATPases