title: Ebola virus matrix protein VP40 uses the COPII transport system for its intracellular transport.
abstract: The Ebola virus matrix protein VP40 plays an important role in virion formation and viral egress from cells. However, the host cell proteins and mechanisms responsible for intracellular transport of VP40 prior to its contribution to virion formation remain to be elucidated. Therefore we used coimmunoprecipitation and mass spectrometric analyses to identify host proteins interacting with VP40. We found that Sec24C, a component of the host COPII vesicular transport system, interacts specifically with VP40 via VP40 amino acids 303 to 307. Coimmunoprecipitation and dominant-negative mutant studies indicated that the COPII transport system plays a critical role in VP40 intracellular transport to the plasma membrane. Marburg virus VP40 was also shown to use the COPII transport system for intracellular transport. These findings identify a conserved intersection between a host pathway and filovirus replication, an intersection that can be targeted in the development of new antiviral drugs.
authors.affiliation: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Shirokanedai, Tokyo 108-8639, Japan.
authors.forename: Seiya
authors.initials: S
authors.lastname: Yamayoshi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Noda
authors.forename: Hideki
authors.initials: H
authors.lastname: Ebihara
authors.forename: Hideo
authors.initials: H
authors.lastname: Goto
authors.forename: Yuko
authors.initials: Y
authors.lastname: Morikawa
authors.forename: Igor S
authors.initials: IS
authors.lastname: Lukashevich
authors.forename: Gabriele
authors.initials: G
authors.lastname: Neumann
authors.forename: Heinz
authors.initials: H
authors.lastname: Feldmann
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawaoka
mesh_terms: D022181:COP-Coated Vesicles / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry; D003600:Cytosol / Q000737:chemistry; D029043:Ebolavirus / Q000502:physiology*; D006801:Humans; D047468:Immunoprecipitation; D029024:Marburgvirus / Q000502:physiology; D013058:Mass Spectrometry; D009698:Nucleoproteins / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D021381:Protein Transport; D033921:Vesicular Transport Proteins / Q000378:metabolism*; D014758:Viral Core Proteins / Q000378:metabolism*
chemical_list: D009698:Nucleoproteins; C530640:SEC24C protein, human; D033921:Vesicular Transport Proteins; D014758:Viral Core Proteins; C084819:nucleoprotein VP40, Ebola virus