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Investigating Ebola virus pathogenicity using Molecular Dynamics

Pappalardo, Morena, Collu, Francesca, Macpherson, James, Michaelis, Martin, Fraternali, Franca, Wass, Mark N. (2017) Investigating Ebola virus pathogenicity using Molecular Dynamics. BMC Genomics, 18 . Article Number 566. ISSN 1471-2164. (doi:10.1186/s12864-017-3912-2) (KAR id:61897)

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Abstract

Background: Ebolaviruses have been known to cause deadly disease in humans for 40 years and have recently been demonstrated in West Africa to be able to cause large outbreaks. Four Ebolavirus species cause severe disease associated with high mortality in humans. Reston viruses are the only Ebolaviruses that do not cause disease in humans. Conserved amino acid changes in the Reston virus protein VP24 compared to VP24 of other Ebolaviruses have been suggested to alter VP24 binding to host cell karyopherins resulting in impaired inhibition of interferon signalling, which may explain the difference in human pathogenicity. Here we used protein structural analysis and molecular dynamics to further elucidate the interaction between VP24 and KPNA5. Results: As a control experiment, we compared the interaction of wild-type and R137A-mutant (known to affect KPNA5 binding) Ebola virus VP24 with KPNA5. Results confirmed that the R137A mutation weakens direct VP24-KPNA5 binding and enables water molecules to penetrate at the interface. Similarly, Reston virus VP24 displayed a weaker interaction with KPNA5 than Ebola virus VP24, which is likely to reduce the ability of Reston virus VP24 to prevent host cell interferon signalling. Conclusion: Our results provide novel molecular detail on the interaction of Reston virus VP24 and Ebola virus VP24 with human KPNA5. The results indicate a weaker interaction of Reston virus VP24 with KPNA5 than Ebola virus VP24, which is probably associated with a decreased ability to interfere with the host cell interferon response. Hence, our study provides further evidence that VP24 is a key player in determining Ebolavirus pathogenicity.

Item Type: Article
DOI/Identification number: 10.1186/s12864-017-3912-2
Uncontrolled keywords: Ebola virus, molecular dynamics, virus pathogenicity, structural bioinformatics
Subjects: Q Science > Q Science (General)
Divisions: Divisions > Division of Natural Sciences > Biosciences
Depositing User: Mark Wass
Date Deposited: 31 May 2017 11:05 UTC
Last Modified: 10 Dec 2022 14:57 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/61897 (The current URI for this page, for reference purposes)

University of Kent Author Information

Pappalardo, Morena.

Creator's ORCID:
CReDIT Contributor Roles:

Michaelis, Martin.

Creator's ORCID: https://orcid.org/0000-0002-5710-5888
CReDIT Contributor Roles:

Wass, Mark N..

Creator's ORCID: https://orcid.org/0000-0001-5428-6479
CReDIT Contributor Roles:
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