Brandon Lookfong

Background:  The Ebola virus is a non-segmented negative sense RNA virus that has caused multiple outbreaks in the last century [1-3]. The hemorrhagic fever, multi system organ failure, and cardiac dysfunction along with the high transmissibility of the virus in bodily fluids lead to fatality rates up to 53.72% [3]. The virus is comprised of seven genomes with most of the viruses infectability and morbidity stemming from the Ebola Virus Glycoprotein (EBGP)[1]. EBGP serves important functions in viral infiltration, immune system evasion, immune system activation, and pathogenesis.

Methods:  A literature review utilizing the PUBMED data base was conducted to elucidate the role of Ebola Virus Glycoprotein on infectability. A comprehensive background was found using review articles. Additional search terms included “EBGP”, “EBOV “glycoprotein”, and “Ebola virus genome” specific for primary research articles focusing on EBGP.

Results:  From the literature search it was found that through the high affinity of TIM-1 and DC-SIGNR host cell receptors to the Ebola Virus Glycoprotein, the virus can attach and induce endocytosis of the viral particle[4 5]. This was determined through the use of atomic force microscopy and research showed the TIM-1 receptor was especially correlated to viral infectivity[5]. Moreover, EBGP attachment to the host cell serves as a barrier to the innate immune system as the EBGP also sterically hiders the ability of immune cells to attach to the same host cell[6]. However, as the number of viral particles in the host rises, the attachment of toll Like Receptor 4 to EBGP activates an immune response mediated by macrophages and antigen presenting cells. This induces a vast release of chemokines and cytokines, notability of IL-1β, IL-6, IL-8, and tumor necrosis factor (TNF)[7], which leads to recruitment of other Ebola Virus susceptible cells and the death of lymphocytes[3]. Through this immune response and Ebola Virus Rho/ROCK mediated cytoskeletal remodeling, an increase in vascular permeability occurs which leads to the development of third spacing[8]. Additionally, the immune response causes encephalopathy, hepatocyte injury, fluid and electrolyte balance disorder, acid base disruption, acute kidney injury, skeletal muscle injury, hemorrhage, and ultimately death[2].

Conclusion:  The role of Ebola Virus Glycoprotein in viral infectivity, immune evasion, and morbidity is clear. Consequently, therapeutics targeting this protein have become mainstream with respect to vaccines, and phenotypic revival. Specifically, therapeutics using Ebola virus monoclonal antibodies[9] and testing platforms utilizing organ on a chip technology to simulate a host infected by the virus[8] have been recent innovations.

Works Cited

1. Hoenen T, Groseth A, Feldmann H. Therapeutic strategies to target the Ebola virus life cycle. Nature Reviews Microbiology 2019;17(10):593-606 doi: 10.1038/s41579-019-0233-2.
2. Malvy D, McElroy AK, de Clerck H, Günther S, van Griensven J. Ebola virus disease. The Lancet 2019;393(10174):936-48.
3. Jacob ST, Crozier I, Fischer WA, et al. Ebola virus disease. Nature Reviews Disease Primers 2020;6(1):13 doi: 10.1038/s41572-020-0147-3.
4. Zhang M, Wang X, Hu L, et al. TIM-1 augments cellular entry of Ebola virus species and mutants, which is blocked by recombinant TIM-1 protein. Microbiology Spectrum 2022;10(3):e02212-21.
5. Zhang Q, Yang J, Tillieux S, et al. Stepwise Enzymatic-Dependent Mechanism of Ebola Virus Binding to Cell Surface Receptors Monitored by AFM. Nano Letters 2022;22(4):1641-48 doi: 10.1021/acs.nanolett.1c04677.
6. Iraqi M, Edri A, Greenshpan Y, et al. N-Glycans mediate the ebola virus-GP1 shielding of ligands to immune receptors and immune evasion. Frontiers in cellular and infection microbiology 2020;10:48.
7. Lai C-Y, Strange DP, Wong TAS, Lehrer AT, Verma S. Ebola virus glycoprotein induces an innate immune response in vivo via TLR4. Frontiers in microbiology 2017;8:1571.
8. Junaid A, Tang H, van Reeuwijk A, et al. Ebola Hemorrhagic Shock Syndrome-on-a-Chip. iScience 2020;23(1):100765 doi: https://doi.org/10.1016/j.isci.2019.100765.
9. Saphire EO, Schendel SL, Fusco ML, et al. Systematic analysis of monoclonal antibodies against Ebola virus GP defines features that contribute to protection. Cell 2018;174(4):938-52. e13.