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Phosphatidylserine clustering by the Ebola virus matrix protein is a critical step in viral budding
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 dru...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9638875/ https://www.ncbi.nlm.nih.gov/pubmed/36094794 http://dx.doi.org/10.15252/embr.202051709 |
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author | Husby, Monica L Amiar, Souad Prugar, Laura I David, Emily A Plescia, Caroline B Huie, Kathleen E Brannan, Jennifer M Dye, John M Pienaar, Elsje Stahelin, Robert V |
author_facet | Husby, Monica L Amiar, Souad Prugar, Laura I David, Emily A Plescia, Caroline B Huie, Kathleen E Brannan, Jennifer M Dye, John M Pienaar, Elsje Stahelin, Robert V |
author_sort | Husby, Monica L |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9638875 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-96388752022-11-14 Phosphatidylserine clustering by the Ebola virus matrix protein is a critical step in viral budding Husby, Monica L Amiar, Souad Prugar, Laura I David, Emily A Plescia, Caroline B Huie, Kathleen E Brannan, Jennifer M Dye, John M Pienaar, Elsje Stahelin, Robert V EMBO Rep Articles 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. John Wiley and Sons Inc. 2022-09-12 /pmc/articles/PMC9638875/ /pubmed/36094794 http://dx.doi.org/10.15252/embr.202051709 Text en © 2022 The Authors. Published under the terms of the CC BY NC ND 4.0 license. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Articles Husby, Monica L Amiar, Souad Prugar, Laura I David, Emily A Plescia, Caroline B Huie, Kathleen E Brannan, Jennifer M Dye, John M Pienaar, Elsje Stahelin, Robert V Phosphatidylserine clustering by the Ebola virus matrix protein is a critical step in viral budding |
title | Phosphatidylserine clustering by the Ebola virus matrix protein is a critical step in viral budding |
title_full | Phosphatidylserine clustering by the Ebola virus matrix protein is a critical step in viral budding |
title_fullStr | Phosphatidylserine clustering by the Ebola virus matrix protein is a critical step in viral budding |
title_full_unstemmed | Phosphatidylserine clustering by the Ebola virus matrix protein is a critical step in viral budding |
title_short | Phosphatidylserine clustering by the Ebola virus matrix protein is a critical step in viral budding |
title_sort | phosphatidylserine clustering by the ebola virus matrix protein is a critical step in viral budding |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9638875/ https://www.ncbi.nlm.nih.gov/pubmed/36094794 http://dx.doi.org/10.15252/embr.202051709 |
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