Phosphatidylserine clustering by the Ebola virus matrix protein is a critical step in viral budding |
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| Authors: | Monica L Husby Souad Amiar Laura I Prugar Emily A David Caroline B Plescia Kathleen E Huie Jennifer M Brannan John M Dye Elsje Pienaar Robert V Stahelin |
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| Affiliation: | 1. Department of Medicinal Chemistry & Molecular Pharmacology, Purdue University, West Lafayette IN, USA ; 2. Purdue Institute of Inflammation, Immunology and Infectious Disease (PI4D), Purdue University, West Lafayette, West Lafayette IN, USA ; 3. United States Army Medical Research Institute of Infectious Diseases USAMRIID, Fort Detrick, Frederick MD, USA ; 4. Weldon School of Biomedical Engineering, Purdue University, West Lafayette IN, USA |
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| Abstract: | Phosphatidylserine (PS) is a critical lipid factor in the assembly and spread of numerous lipid‐enveloped viruses. Here, we describe the ability of the Ebola virus (EBOV) matrix protein eVP40 to induce clustering of PS and promote viral budding in vitro, as well as the ability of an FDA‐approved drug, fendiline, to reduce PS clustering and subsequent virus budding and entry. To gain mechanistic insight into fendiline inhibition of EBOV replication, multiple in vitro assays were run including imaging, viral budding and viral entry assays. Fendiline lowers PS content in mammalian cells and PS in the plasma membrane, where the ability of VP40 to form new virus particles is greatly lower. Further, particles that form from fendiline‐treated cells have altered particle morphology and cannot significantly infect/enter cells. These complementary studies reveal the mechanism by which EBOV matrix protein clusters PS to enhance viral assembly, budding, and spread from the host cell while also laying the groundwork for fundamental drug targeting strategies. |
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| Keywords: | Ebola virus matrix protein phosphatidylserine plasma membrane viral budding |
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