Structural and Functional Aspects of Ebola Virus Proteins

Overview

Journal Pathogens

Date 2021 Oct 23

PMID 34684279

Citations 19

Authors

Sahil Jain

Ekaterina Martynova

Albert Rizvanov

Svetlana Khaiboullina

Manoj Baranwal

Affiliations

Soon will be listed here.

Abstract

Ebola virus (EBOV), member of genus , family , have a non-segmented, single-stranded RNA that contains seven genes: (a) nucleoprotein (NP), (b) viral protein 35 (VP35), (c) VP40, (d) glycoprotein (GP), (e) VP30, (f) VP24, and (g) RNA polymerase (L). All genes encode for one protein each except GP, producing three pre-proteins due to the transcriptional editing. These pre-proteins are translated into four products, namely: (a) soluble secreted glycoprotein (sGP), (b) Δ-peptide, (c) full-length transmembrane spike glycoprotein (GP), and (d) soluble small secreted glycoprotein (ssGP). Further, shed GP is released from infected cells due to cleavage of GP by tumor necrosis factor α-converting enzyme (TACE). This review presents a detailed discussion on various functional aspects of all EBOV proteins and their residues. An introduction to ebolaviruses and their life cycle is also provided for clarity of the available analysis. We believe that this review will help understand the roles played by different EBOV proteins in the pathogenesis of the disease. It will help in targeting significant protein residues for therapeutic and multi-protein/peptide vaccine development.

Citing Articles

Algal Lectin Griffithsin Inhibits Ebola Virus Infection.

Wang L, Alfson K, Eaton B, Mattix M, Goez-Gazi Y, Holbrook M Molecules. 2025; 30(4).

PMID: 40005201 PMC: 11858388. DOI: 10.3390/molecules30040892.

Discovery of Thiophene Derivatives as Potent, Orally Bioavailable, and Blood-Brain Barrier-Permeable Ebola Virus Entry Inhibitors.

Morales-Tenorio M, Lasala F, Garcia-Rubia A, Aledavood E, Heung M, Olal C J Med Chem. 2024; 67(18):16381-16402.

PMID: 39248591 PMC: 11440591. DOI: 10.1021/acs.jmedchem.4c01267.

Rational design of self-amplifying virus-like vesicles with Ebola virus glycoprotein as vaccines.

Zhang H, Zhang Y, Deng C, Zhu Q, Zhang Z, Li X Mol Ther. 2024; 32(10):3695-3711.

PMID: 39217415 PMC: 11489537. DOI: 10.1016/j.ymthe.2024.08.026.

National burden of Ebola virus disease in Democratic Republic of the Congo: the urgency to act.

Ahmad B, Sagide M, Ntamwinja S, Byiringiro E, Kihanduka E, Rugendabanga E Ann Med Surg (Lond). 2024; 86(8):4579-4585.

PMID: 39118744 PMC: 11305799. DOI: 10.1097/MS9.0000000000002213.

Efficient SARS-CoV-2 variant detection and monitoring with Spike Screen next-generation sequencing.

Suljic A, Zorec T, Zakotnik S, Vlaj D, Kogoj R, Knap N Brief Bioinform. 2024; 25(4).

PMID: 38833323 PMC: 11149657. DOI: 10.1093/bib/bbae263.

References

Escudero-Perez B, Volchkova V, Dolnik O, Lawrence P, Volchkov V . Shed GP of Ebola virus triggers immune activation and increased vascular permeability. PLoS Pathog. 2014; 10(11):e1004509. PMC: 4239094. DOI: 10.1371/journal.ppat.1004509. View

Warren T, Whitehouse C, Wells J, Welch L, Heald A, Charleston J . A single phosphorodiamidate morpholino oligomer targeting VP24 protects rhesus monkeys against lethal Ebola virus infection. mBio. 2015; 6(1). PMC: 4337572. DOI: 10.1128/mBio.02344-14. View

Han Z, Harty R . Packaging of actin into Ebola virus VLPs. Virol J. 2005; 2:92. PMC: 1334228. DOI: 10.1186/1743-422X-2-92. View

Ruthel G, Demmin G, Kallstrom G, Javid M, Badie S, Will A . Association of ebola virus matrix protein VP40 with microtubules. J Virol. 2005; 79(8):4709-19. PMC: 1069569. DOI: 10.1128/JVI.79.8.4709-4719.2005. View

Jain S, Khaiboullina S, Baranwal M . Immunological Perspective for Ebola Virus Infection and Various Treatment Measures Taken to Fight the Disease. Pathogens. 2020; 9(10). PMC: 7603231. DOI: 10.3390/pathogens9100850. View

Johnson K, Pokhrel R, Budicini M, Gerstman B, Chapagain P, Stahelin R . A Conserved Tryptophan in the Ebola Virus Matrix Protein C-Terminal Domain Is Required for Efficient Virus-Like Particle Formation. Pathogens. 2020; 9(5). PMC: 7281420. DOI: 10.3390/pathogens9050402. View

Halfmann P, Neumann G, Kawaoka Y . The Ebolavirus VP24 protein blocks phosphorylation of p38 mitogen-activated protein kinase. J Infect Dis. 2011; 204 Suppl 3:S953-6. PMC: 3189987. DOI: 10.1093/infdis/jir325. View

Adu-Gyamfi E, Digman M, Gratton E, Stahelin R . Investigation of Ebola VP40 assembly and oligomerization in live cells using number and brightness analysis. Biophys J. 2012; 102(11):2517-25. PMC: 3368128. DOI: 10.1016/j.bpj.2012.04.022. View

Martin B, Coutard B, Guez T, Paesen G, Canard B, Debart F . The methyltransferase domain of the Sudan ebolavirus L protein specifically targets internal adenosines of RNA substrates, in addition to the cap structure. Nucleic Acids Res. 2018; 46(15):7902-7912. PMC: 6125687. DOI: 10.1093/nar/gky637. View

10.

Wang B, Wang Y, Frabutt D, Zhang X, Yao X, Hu D . Mechanistic understanding of -glycosylation in Ebola virus glycoprotein maturation and function. J Biol Chem. 2017; 292(14):5860-5870. PMC: 5392578. DOI: 10.1074/jbc.M116.768168. View

11.

Dong S, Yang P, Li G, Liu B, Wang W, Liu X . Insight into the Ebola virus nucleocapsid assembly mechanism: crystal structure of Ebola virus nucleoprotein core domain at 1.8 Å resolution. Protein Cell. 2015; 6(5):351-62. PMC: 4417675. DOI: 10.1007/s13238-015-0163-3. View

12.

ELLIOTT L, Kiley M, McCormick J . Descriptive analysis of Ebola virus proteins. Virology. 1985; 147(1):169-76. DOI: 10.1016/0042-6822(85)90236-3. View

13.

Wendt L, Brandt J, Bodmer B, Reiche S, Schmidt M, Traeger S . The Ebola Virus Nucleoprotein Recruits the Nuclear RNA Export Factor NXF1 into Inclusion Bodies to Facilitate Viral Protein Expression. Cells. 2020; 9(1). PMC: 7017048. DOI: 10.3390/cells9010187. View

14.

Weik M, Enterlein S, Schlenz K, Muhlberger E . The Ebola virus genomic replication promoter is bipartite and follows the rule of six. J Virol. 2005; 79(16):10660-71. PMC: 1182658. DOI: 10.1128/JVI.79.16.10660-10671.2005. View

15.

Jain S, Baranwal M . Conserved peptide vaccine candidates containing multiple Ebola nucleoprotein epitopes display interactions with diverse HLA molecules. Med Microbiol Immunol. 2019; 208(2):227-238. DOI: 10.1007/s00430-019-00584-y. View

16.

Empig C, Goldsmith M . Association of the caveola vesicular system with cellular entry by filoviruses. J Virol. 2002; 76(10):5266-70. PMC: 136134. DOI: 10.1128/jvi.76.10.5266-5270.2002. View

17.

Jeffers S, Sanders D, Sanchez A . Covalent modifications of the ebola virus glycoprotein. J Virol. 2002; 76(24):12463-72. PMC: 136726. DOI: 10.1128/jvi.76.24.12463-12472.2002. View

18.

Pappalardo M, Reddin I, Cantoni D, Rossman J, Michaelis M, Wass M . Changes associated with Ebola virus adaptation to novel species. Bioinformatics. 2017; 33(13):1911-1915. DOI: 10.1093/bioinformatics/btx065. View

19.

Feldmann H, Sprecher A, Geisbert T . Ebola. N Engl J Med. 2020; 382(19):1832-1842. DOI: 10.1056/NEJMra1901594. View

20.

Francica J, Varela-Rohena A, Medvec A, Plesa G, Riley J, Bates P . Steric shielding of surface epitopes and impaired immune recognition induced by the ebola virus glycoprotein. PLoS Pathog. 2010; 6(9):e1001098. PMC: 2936550. DOI: 10.1371/journal.ppat.1001098. View