Author:
Liu Xiao,Stahelin Robert V.,Pienaar Elsje
Abstract
AbstractEbola virus (EBOV) protein VP40 can assemble and bud in the form of virus-like particles (VLPs) when expressed in the absence of other EBOV proteins in mammalian cells. When nucleoprotein (NP) is co-expressed, VLPs will contain inclusion-body (IB) cores, and VLP production can be increased. However, the mechanism of how NP impacts VLP production remains unclear. Here, we use a computational approach to study NP-VP40 interactions. We find that NP may enhance VLP production through stabilizing VP40 filaments and accelerating the VLP budding step. Also, both the relative timing and amount of NP expression compared to VP40 are important for the effective production of IB-containing VLPs. We further find that there exists an optimum NP/VP40 expression ratio, and that earlier expression of NP compared to VP40 will produce IB-containing VLPs more efficiently. We conclude that disrupting the relative timing and amount of NP and VP40 expression could provide new avenues to treat EBOV infection. This work provides quantitative insights into how EBOV proteins interact and how those interactions could impact virion generation and drug efficacy.
Publisher
Cold Spring Harbor Laboratory
Reference39 articles.
1. The ecology of Ebola virus
2. Ebola Hemorrhagic Fever: Novel Biomarker Correlates of Clinical Outcome
3. Ebola Virus Disease Distribution Map: Cases of Ebola Virus Disease in Africa Since 1976 | History | Ebola (Ebola Virus Disease) | CDC (2021) [online] https://www.cdc.gov/vhf/ebola/history/distribution-map.html (Accessed February 23, 2023)
4. Ebola: A Hyperinflated Emergency
5. Monoclonal Antibody Approved to Treat Ebola;American Journal of Nursing,2021