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The Ebola Virus Matrix Protein VP40 Interacts Selectively with Plasma Membrane Lipids to Promote Viral Egress
Author(s) -
Vecchio Kathryn Del,
Shwarz Anna,
Saphire Erica Ollmann,
Stahelin Robert
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.945.1
Subject(s) - vp40 , ebola virus , viral matrix protein , microbiology and biotechnology , phosphatidylserine , marburg virus , biology , ebolavirus , viral protein , chemistry , virology , virus , biochemistry , membrane , phospholipid
Filoviruses are filamentous viruses and include Ebola (EBOV) and Marburg (MARV), which are morphologically identical but antigenically distinct. Mortality rates can be has high as 90% and to date there are no FDA approved vaccines or small molecules for treatment outside the realm of emergency situations under the compassionate use clauses of FDA policy. EBOV harbors a genome of 7 proteins, the most abundantly expressed in mature virions is Viral Protein 40 (VP40) also known as the matrix protein. VP40 is required for the assembly and budding of EBOV and alone VP40 can form virus like particles (VLPs) from the plasma membrane of host cells. Recent work by the Stahelin and Ollmann Saphire labs indicates that VP40 adopts multiple different structures to elicit different functions in the viral life cycle. Cellular data demonstrates that each structure adopts a specific function, one for budding form the plasma membrane of human cells and one for regulation of viral transcription. This work investigates how distinct VP40 structures assemble in the presence of synthetic lipid vesicles and at the inner leaflet of the plasma membrane in live cells. This project aims to determine lipid composition requirements for functionality of VP40 mutants vs. wild‐type VP40, and to elucidate the function of VP40 oligomerization with site‐specific mutants. The C‐terminal domains of the VP40 homodimer exhibit a highly conserved basic patch which is thought to promote interaction with anionic lipids. Preliminary data confirms that VP40 binds with nanomolar affinity to liposomes containing phosphatidylserine (PS), an anionic lipid found within the inner leaflet of the plasma membrane, and has specificity for this anionic lipid in particular. Cellular data from the Stahelin lab provides precedent that VP40 requires PS in order to bud from the plasma membrane. Lipidomics analysis of mammalian cells transfected with VP40 has aided in the investigation of the species and saturation of lipid populations of in the plasma membrane versus lipid populations in VLPs. Preliminary data suggest that VP40 selects for not only specific species of lipids, but for particular saturation states of lipids within the plasma membrane. Support or Funding Information This work has been supported by NIH grant AI081077 and NIH grant T32GM075762.