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

Kristen A. Johnson, Geoffrey J F Taghon, Jordan L. Scott, Robert Stahelin

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number19125
JournalScientific Reports
Volume6
DOIs
StatePublished - Jan 12 2016

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Ebolavirus
Phosphatidylinositols
Cell Membrane
Virion
Proteins
Virus Assembly
Phosphatidylserines
Membranes
Infection

ASJC Scopus subject areas

  • General

Cite this

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.

In: Scientific Reports, Vol. 6, 19125, 12.01.2016.

Research output: Contribution to journalArticle

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