Bulletin of ANPA
Abstract submitted to ANPA Conference July 14–16, 2023
Volume 5, Number 1
Biological, Medical, Soft Matter and Chemical Physics
Abstract ID: ANPA2023-N00034
Abstract:
ANPA2023-N00034: Role of Lipid Composition on Ebola Virus Matrix Protein VP40 Interactions with the Human Plasma Membrane
Authors:
- Michael D. Cioffi; Florida International University
- Bernard S. Gerstman; Florida International University
- Prem P. Chapagain;
The Ebola virus is a highly dangerous virus which can cause severe hemorrhagic fever in humans leading to high fatality rates. The Ebola virus matrix protein VP40 is the major protein responsible for the formation of the viral matrix by localizing and assembling it at the inner leaflet of the human plasma membrane (PM). This assembly leads to the formation of virus-like-particles (VLP) and eventual budding. Anionic lipids PI(4,5)P2 (PIP2) and Phosphatidylserine (PS) have been shown to facilitate VP40-PM binding through electrostatic interactions with cationic VP40 residues. It has been determined that Phosphatidic Acid (PA), resulting from the enzyme Phospholipase-D (PLD), may also play an active role in this process. We performed coarse-grained molecular dynamics (CGMD) simulations to investigate the effects various lipids have on VP40-lipid interactions. We used a triple-dimer structure of VP40 and a PM composed of various lipid types. Contact analyses show interactions with specific cationic VP40 residues that facilitate most of the lipid interactions. Interaction strengths between VP40 residues and lipid headgroups are found to vary when PA was included in the PM compared to when it was not. Radial distribution functions also show differences in local lipid clustering when PA was introduced into the PM. These simulations provide new insights on multi-dimer VP40 interactions with the human PM and how different lipid compositions may influence overall membrane association.
To cite this abstract, use the following reference: https://anpaglobal.org/conference/2023/ANPA2023-N00034