Presentation Title: Computational Model of Ebolavirus Matrix Protein Assembly: Phospholipid Influence on Production of Viral Particles
Author Name(s): Authors: Liu X1,*, Pappas E1, Husby ML2, Stahelin RV2, Pienaar E1
Author Department and School Affiliation: 1Weldon School of Biomedical Engineering, 2Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University
Abstract: Ebola virus (EBOV) causes severe hemorrhagic fever in humans, with up to 90% mortality rates without treatment[1]. EBOV studies are limited by the BSL4 requirement for work with live viruses. However, EBOV matrix protein VP40 alone can assemble into virus-like particles (VLPs)[2], making it a useful model system for studying EBOV budding processes in BSL2 facilities. To study VLP dynamics, and evaluate phosphatidylserine-targeted treatment, we built an ODE-based mathematical model of the VP40 system. Phosphatidylserine plays an important role in VLP budding[3,4], and our model predicts that it most strongly affects binding of VP40 dimer to cell membrane, budding of mature filaments as well as stabilization of filaments. Stabilization of filaments has not been shown for EBOV, but similar mechanisms have been identified in oligomerization of microtubules[5]. Our results also suggest that the effect of PS on budding depends on the state of the system and the parameter space, which explains why the decrease of PS in some, but not all, experiments leads to decrease of VLP. The model is poised to consider additional viral proteins, more cell component interactions, dose-response predictions for drugs that affect membrane PS concentration, and mechanism identification for drug discovery in parallel with experimental studies.
References:
[1] Banadyga, L., et al. (2017). Scientific reports, 7(1), 1-14.
[2] Stahelin, R. V. (2014). Frontiers in microbiology, 5, 300.
[3] Adu-Gyamfi, E., et al (2015). Journal of virology, 89(18), 9440-9453.
[4] Adu-Gyamfi, E., et al (2013). Journal of Biological Chemistry, 288(8), 5779-5789.
[5] Job, D., et al. (2003). Current opinion in cell biology, 15(1), 111-117.
