title: The Ebola virus matrix protein VP40 selectively induces vesiculation from phosphatidylserine-enriched membranes.
abstract: Ebola virus is from the Filoviridae family of viruses and is one of the most virulent pathogens known with ∼ 60% clinical fatality. The Ebola virus negative sense RNA genome encodes seven proteins including viral matrix protein 40 (VP40), which is the most abundant protein found in the virions. Within infected cells VP40 localizes at the inner leaflet of the plasma membrane (PM), binds lipids, and regulates formation of new virus particles. Expression of VP40 in mammalian cells is sufficient to form virus-like particles that are nearly indistinguishable from the authentic virions. However, how VP40 interacts with the PM and forms virus-like particles is for the most part unknown. To investigate VP40 lipid specificity in a model of viral egress we employed giant unilamellar vesicles with different lipid compositions. The results demonstrate VP40 selectively induces vesiculation from membranes containing phosphatidylserine (PS) at concentrations of PS that are representative of the PM inner leaflet content. The formation of intraluminal vesicles was not significantly detected in the presence of other important PM lipids including cholesterol and polyvalent phosphoinositides, further demonstrating PS selectivity. Taken together, these studies suggest that PM phosphatidylserine may be an important component of Ebola virus budding and that VP40 may be able to mediate PM scission.
authors.affiliation: From the Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, South Bend, Indiana 46617 and.
authors.forename: Smita P
authors.initials: SP
authors.lastname: Soni
authors.affiliation: From the Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, South Bend, Indiana 46617 and the Department of Chemistry and Biochemistry and the Eck Institute for Global Health, University of Notre Dame, Notre Dame, Indiana 46556 rstaheli@iu.edu.
authors.forename: Robert V
authors.initials: RV
authors.lastname: Stahelin
mesh_terms: D029043:Ebolavirus / Q000737:chemistry* / Q000378:metabolism; D008567:Membranes, Artificial; D008954:Models, Biological; D010718:Phosphatidylserines / Q000737:chemistry* / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000737:chemistry* / Q000378:metabolism; D057074:Virus Release / Q000502:physiology
chemical_list: D008567:Membranes, Artificial; D010718:Phosphatidylserines; C080981:VP40 protein, virus; D014763:Viral Matrix Proteins
keywords: Ebola Virus; Giant Unilammelar Vesicles; Lipid Binding Protein; Matrix Protein; Membrane Budding; Phosphatidylserine; VP40; Viral Budding; Viral Protein; Virus Assembly