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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
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.
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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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