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The Ebola Virus Matrix Protein and Membrane Fluidity
Author(s) -
Johnson Kristen A,
Stahelin Robert V
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.630.5
Subject(s) - ebola virus , vp40 , viral matrix protein , membrane fluidity , membrane , virus , microbiology and biotechnology , lipid bilayer , phosphatidylinositol 4,5 bisphosphate , chemistry , viral membrane , ebolavirus , biology , virology , biophysics , phosphatidylinositol , biochemistry , viral envelope , signal transduction
While the Ebola virus is considered a rare and neglected disease, it received worldwide attention during the 2014–15 epidemic. This recent outbreak was eleven times larger than all previous Ebola virus outbreaks combined, taking a large toll on the lives and economies of Western Africa. Unfortunately, there are still no FDA approved therapeutics or vaccines for Ebola virus treatment. The most abundant protein of the virus, which was also the most conserved in amino acid sequence during the course of the outbreak, is the matrix protein VP40. VP40 is sufficient to form virus like particles from human cells independent of other viral proteins and has been suggested to be viable therapeutic target. We aim to better understand how VP40 is able to interact with lipid membranes consisting of different glycerophospholipids and sphingolipids and bend them to form the virus particle. The Stahelin lab has found that VP40 requires the anionic lipids phosphatidylserine (PS) and phosphatidylinositol (4,5)bisphosphate (PI(4,5)P 2 ) at the plasma membrane for proper assembly. We are now investigating if the physical property of membrane fluidity plays a roll in VP40 function. Objective We are implementing several assays to investigate the role of membrane fluidity in VP40 membrane binding, oligomerization, and membrane bending. Methods Confocal Laser Scanning Microscopy (CLSM), Number and Brightness analysis (N&B), Liposome Pelleting Assays, and Transmission Electron Microscopy (TEM). Results VP40 assembly is sensitive to membrane fluidity and has greater binding to ordered membranes than disordered membranes. When membrane fluidity is changed in cells, VP40 localization and large oligomers at the plasma membrane disassemble. We have identified FDA approved drugs that modulate membrane fluidity and are testing their efficacy against VP40 function. Conclusions This project aims to better understand VP40 membrane binding and bending functions in relation to membrane fluidity. We have observed that VP40 function is sensitive to changes in membrane fluidity in vitro and in live cells. We hope that a deeper understanding of VP40 dependency on membrane fluidity will allow for expedited drug discovery or reapplication of FDA Approved drugs. Support or Funding Information Financial Support: NIH AI081077