The Ebola Virus Matrix Protein Bends Biological Membranes

Abstract

Ebola is one of the most virulent pathogen that causes severe hemorrhagic fever with fatality rate as high as 90%. There is an urgency in the development of treatment as there are no known drugs or vaccines approved by the FDA and the virus poses a serious health and potential biological threat. The Ebola viral matrix protein 40 (VP40), is the most abundantly express protein of the viurs and alone harbors the ability to form virus like particles (VLPs) that are indistinguishable from the authentic virus. The mechanism of VP40 assembly at the plasma membrane before the release of the virions remains poorly understood. In order to better understand the process of viral egress, it is crucial to understand how VP40 is able to bend the plasma membrane to regulate formation of VLPs. Here we take a detailed look at how VP40 alone is able to bend giant unilamellar vesicles (GUVs) membranes, a model for VLP egress. Here, we imaged GUV's containing PC:PE with and without anionic lipids enriched in the plasma membrane such as PS and phosphoinositides to determine VP40 budding selectivity. The results demonstrate PS-dependent bending and vesiculation from GUV's membrane. The vesiculation is not enhanced in the presence of cholesterol and completely inhibited in GUVs composed of polyvalent phosphoinositides. In concert with budding from live human cell models, the bending and VLP formation is unique to PS containing membranes. GUVs have previously been utilized to understand membrane scission and to expose the role of viral proteins in membrane bending. Elucidating the effect of VP40 on GUVs composed of lipids that mimic biological membranes will help understand the mechanistic details of an otherwise illusive membrane remodeler.