title: The Ebola Virus matrix protein, VP40, requires phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) for extensive oligomerization at the plasma membrane and viral egress.
abstract: VP40 is one of eight proteins encoded by the Ebola Virus (EBOV) and serves as the primary matrix protein, forming virus like particles (VLPs) from mammalian cells without the need for other EBOV proteins. While VP40 is required for viral assembly and budding from host cells during infection, the mechanisms that target VP40 to the plasma membrane are not well understood. Phosphatidylserine is required for VP40 plasma membrane binding, VP40 hexamer formation, and VLP egress, However, PS also becomes exposed on the outer membrane leaflet at sites of VP40 budding, raising the question of how VP40 maintains an interaction with the plasma membrane inner leaflet when PS is flipped to the opposite side. To address this question, cellular and in vitro assays were employed to determine if phosphoinositides are important for efficient VP40 localization to the plasma membrane. Cellular studies demonstrated that PI(4,5)P2 was an important component of VP40 assembly at the plasma membrane and subsequent virus like particle formation. Additionally, PI(4,5)P2 was required for formation of extensive oligomers of VP40, suggesting PS and PI(4,5)P2 have different roles in VP40 assembly where PS regulates formation of hexamers from VP40 dimers and PI(4,5)P2 stabilizes and/or induces extensive VP40 oligomerization at the plasma membrane.
authors.affiliation: Department of Chemistry and Biochemistry, the Eck Institute for Global Health, and the Boler-Parseghian Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, Indiana, 46556.
authors.forename: Kristen A
authors.initials: KA
authors.lastname: Johnson
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine-South Bend, South Bend, Indiana 46617.
authors.forename: Geoffrey J F
authors.initials: GJ
authors.lastname: Taghon
authors.affiliation: Department of Chemistry and Biochemistry, the Eck Institute for Global Health, and the Boler-Parseghian Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, Indiana, 46556.
authors.forename: Jordan L
authors.initials: JL
authors.lastname: Scott
authors.affiliation: Department of Chemistry and Biochemistry, the Eck Institute for Global Health, and the Boler-Parseghian Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, Indiana, 46556.|Department of Biochemistry and Molecular Biology, Indiana University School of Medicine-South Bend, South Bend, Indiana 46617.
authors.forename: Robert V
authors.initials: RV
authors.lastname: Stahelin
mesh_terms: D000818:Animals; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism*; D002522:Chlorocebus aethiops; D029043:Ebolavirus / Q000378:metabolism*; D008055:Lipids / Q000737:chemistry; D009698:Nucleoproteins / Q000378:metabolism*; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism*; D011485:Protein Binding; D055503:Protein Multimerization; D055672:Static Electricity; D014758:Viral Core Proteins / Q000378:metabolism*; D057074:Virus Release
chemical_list: D008055:Lipids; D009698:Nucleoproteins; D019269:Phosphatidylinositol 4,5-Diphosphate; D014758:Viral Core Proteins; C084819:nucleoprotein VP40, Ebola virus