Conserved differences in protein sequence determine the human pathogenicity of Ebolaviruses.

Pappalardo, Morena and Juliá, Miguel and Howard, Mark J. and Rossman, Jeremy S. and Michaelis, Martin and Wass, Mark N. (2016) Conserved differences in protein sequence determine the human pathogenicity of Ebolaviruses. Scientific reports, 6 . p. 23743. ISSN 2045-2322. E-ISSN 2045-2322. (doi:https://doi.org/10.1038/srep23743) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

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Official URL
http://dx.doi.org/10.1038/srep23743

Abstract

Reston viruses are the only Ebolaviruses that are not pathogenic in humans. We analyzed 196 Ebolavirus genomes and identified specificity determining positions (SDPs) in all nine Ebolavirus proteins that distinguish Reston viruses from the four human pathogenic Ebolaviruses. A subset of these SDPs will explain the differences in human pathogenicity between Reston and the other four ebolavirus species. Structural analysis was performed to identify those SDPs that are likely to have a functional effect. This analysis revealed novel functional insights in particular for Ebolavirus proteins VP40 and VP24. The VP40 SDP P85T interferes with VP40 function by altering octamer formation. The VP40 SDP Q245P affects the structure and hydrophobic core of the protein and consequently protein function. Three VP24 SDPs (T131S, M136L, Q139R) are likely to impair VP24 binding to human karyopherin alpha5 (KPNA5) and therefore inhibition of interferon signaling. Since VP24 is critical for Ebolavirus adaptation to novel hosts, and only a few SDPs distinguish Reston virus VP24 from VP24 of other Ebolaviruses, human pathogenic Reston viruses may emerge. This is of concern since Reston viruses circulate in domestic pigs and can infect humans, possibly via airborne transmission.

Item Type: Article
Subjects: Q Science > QR Microbiology > QR355 Virology
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Martin Michaelis
Date Deposited: 06 Apr 2016 17:48 UTC
Last Modified: 08 Sep 2016 11:08 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/54808 (The current URI for this page, for reference purposes)
ORCiD (Michaelis, Martin): http://orcid.org/0000-0002-5710-5888
ORCiD (Wass, Mark N.): http://orcid.org/0000-0001-5428-6479
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