The Ebola Virus Matrix Protein VP40 Selectively Induces Vesiculation from Phosphatidylserine-enriched Membranes

• Published in: The Journal of biological chemistry Vol. 289; no. 48; pp. 33590 - 33597
• Main Authors: Soni, Smita P., Stahelin, Robert V.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 28.11.2014; American Society for Biochemistry and Molecular Biology
• Subjects: Ebola Virus; Ebolavirus - chemistry; Ebolavirus - metabolism; Giant Unilammelar Vesicles; Lipid Binding Protein; Lipids; Matrix Protein; Membrane Budding; Membranes, Artificial; Models, Biological; Phosphatidylserine; Phosphatidylserines - chemistry; Phosphatidylserines - metabolism; Viral Budding; Viral Matrix Proteins - chemistry; Viral Matrix Proteins - metabolism; Viral Protein; Virus Assembly; Virus Release - physiology; VP40; Viral Protein; Membrane Budding; Lipid Binding Protein; Ebola Virus; Giant Unilammelar Vesicles; Viral Budding; Virus Assembly; Matrix Protein; Phosphatidylserine; VP40
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M114.586396

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. Background: Ebola virus VP40 matrix protein is able to produce virus-like particles from cells. Results: VP40 induces negative membrane curvature and scission from in vitro membranes. Conclusion: Phosphatidylserine plays an important role in VP40-induced vesiculation. Significance: Elucidation of VP40 interactions with lipids could lead to a better understanding of the Ebola virus replication cycle.