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The Ebola Virus matrix protein, VP40, requires phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)) for extensive oligomerization at the plasma membrane and viral egress

VP40 is one of eight proteins encoded by the Ebola Virus (EBOV) and serves as the primary matrix protein, forming virus like particles (VLPs) from mammalian cells without the need for other EBOV proteins. While VP40 is required for viral assembly and budding from host cells during infection, the mec...

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Autores principales: Johnson, Kristen A., Taghon, Geoffrey J. F., Scott, Jordan L., Stahelin, Robert V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4709572/
https://www.ncbi.nlm.nih.gov/pubmed/26753796
http://dx.doi.org/10.1038/srep19125
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author Johnson, Kristen A.
Taghon, Geoffrey J. F.
Scott, Jordan L.
Stahelin, Robert V.
author_facet Johnson, Kristen A.
Taghon, Geoffrey J. F.
Scott, Jordan L.
Stahelin, Robert V.
author_sort Johnson, Kristen A.
collection PubMed
description VP40 is one of eight proteins encoded by the Ebola Virus (EBOV) and serves as the primary matrix protein, forming virus like particles (VLPs) from mammalian cells without the need for other EBOV proteins. While VP40 is required for viral assembly and budding from host cells during infection, the mechanisms that target VP40 to the plasma membrane are not well understood. Phosphatidylserine is required for VP40 plasma membrane binding, VP40 hexamer formation, and VLP egress, However, PS also becomes exposed on the outer membrane leaflet at sites of VP40 budding, raising the question of how VP40 maintains an interaction with the plasma membrane inner leaflet when PS is flipped to the opposite side. To address this question, cellular and in vitro assays were employed to determine if phosphoinositides are important for efficient VP40 localization to the plasma membrane. Cellular studies demonstrated that PI(4,5)P(2) was an important component of VP40 assembly at the plasma membrane and subsequent virus like particle formation. Additionally, PI(4,5)P(2) was required for formation of extensive oligomers of VP40, suggesting PS and PI(4,5)P(2) have different roles in VP40 assembly where PS regulates formation of hexamers from VP40 dimers and PI(4,5)P(2) stabilizes and/or induces extensive VP40 oligomerization at the plasma membrane.
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spelling pubmed-47095722016-01-20 The Ebola Virus matrix protein, VP40, requires phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)) for extensive oligomerization at the plasma membrane and viral egress Johnson, Kristen A. Taghon, Geoffrey J. F. Scott, Jordan L. Stahelin, Robert V. Sci Rep Article VP40 is one of eight proteins encoded by the Ebola Virus (EBOV) and serves as the primary matrix protein, forming virus like particles (VLPs) from mammalian cells without the need for other EBOV proteins. While VP40 is required for viral assembly and budding from host cells during infection, the mechanisms that target VP40 to the plasma membrane are not well understood. Phosphatidylserine is required for VP40 plasma membrane binding, VP40 hexamer formation, and VLP egress, However, PS also becomes exposed on the outer membrane leaflet at sites of VP40 budding, raising the question of how VP40 maintains an interaction with the plasma membrane inner leaflet when PS is flipped to the opposite side. To address this question, cellular and in vitro assays were employed to determine if phosphoinositides are important for efficient VP40 localization to the plasma membrane. Cellular studies demonstrated that PI(4,5)P(2) was an important component of VP40 assembly at the plasma membrane and subsequent virus like particle formation. Additionally, PI(4,5)P(2) was required for formation of extensive oligomers of VP40, suggesting PS and PI(4,5)P(2) have different roles in VP40 assembly where PS regulates formation of hexamers from VP40 dimers and PI(4,5)P(2) stabilizes and/or induces extensive VP40 oligomerization at the plasma membrane. Nature Publishing Group 2016-01-12 /pmc/articles/PMC4709572/ /pubmed/26753796 http://dx.doi.org/10.1038/srep19125 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Johnson, Kristen A.
Taghon, Geoffrey J. F.
Scott, Jordan L.
Stahelin, Robert V.
The Ebola Virus matrix protein, VP40, requires phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)) for extensive oligomerization at the plasma membrane and viral egress
title The Ebola Virus matrix protein, VP40, requires phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)) for extensive oligomerization at the plasma membrane and viral egress
title_full The Ebola Virus matrix protein, VP40, requires phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)) for extensive oligomerization at the plasma membrane and viral egress
title_fullStr The Ebola Virus matrix protein, VP40, requires phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)) for extensive oligomerization at the plasma membrane and viral egress
title_full_unstemmed The Ebola Virus matrix protein, VP40, requires phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)) for extensive oligomerization at the plasma membrane and viral egress
title_short The Ebola Virus matrix protein, VP40, requires phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)) for extensive oligomerization at the plasma membrane and viral egress
title_sort ebola virus matrix protein, vp40, requires phosphatidylinositol 4,5-bisphosphate (pi(4,5)p(2)) for extensive oligomerization at the plasma membrane and viral egress
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4709572/
https://www.ncbi.nlm.nih.gov/pubmed/26753796
http://dx.doi.org/10.1038/srep19125
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