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Human Adaptation of Ebola Virus during the West African Outbreak

Urbanowicz, Richard A.; McClure, C. Patrick; Sakuntabhai, Anavaj; Sall, Amadou A.; Kobinger, Gary; Müller, Marcel A.; Holmes, Edward C.; Rey, Félix A.; Simon-Loriere, Etienne; Ball, Jonathan K.

Authors

Richard A. Urbanowicz

Anavaj Sakuntabhai

Amadou A. Sall

Gary Kobinger

Marcel A. Müller

Edward C. Holmes

Félix A. Rey

Etienne Simon-Loriere

JONATHAN BALL jonathan.ball@nottingham.ac.uk
Professor of Molecular Virology



Abstract

The 2013–2016 outbreak of Ebola virus (EBOV) in West Africa was the largest recorded. It began following the cross-species transmission of EBOV from an animal reservoir, most likely bats, into humans, with phylogenetic analysis revealing the cocirculation of several viral lineages. We hypothesized that this prolonged human circulation led to genomic changes that increased viral transmissibility in humans. We generated a synthetic glycoprotein (GP) construct based on the earliest reported isolate and introduced amino acid substitutions that defined viral lineages. Mutant GPs were used to generate a panel of pseudoviruses, which were used to infect different human and bat cell lines. These data revealed that specific amino acid substitutions in the EBOV GP have increased tropism for human cells, while reducing tropism for bat cells. Such increased infectivity may have enhanced the ability of EBOV to transmit among humans and contributed to the wide geographic distribution of some viral lineages.

Citation

Urbanowicz, R. A., McClure, C. P., Sakuntabhai, A., Sall, A. A., Kobinger, G., Müller, M. A., …Ball, J. K. (2016). Human Adaptation of Ebola Virus during the West African Outbreak. Cell, 167(4), 1079-1087.e5. https://doi.org/10.1016/j.cell.2016.10.013

Journal Article Type Article
Acceptance Date Oct 6, 2016
Online Publication Date Nov 3, 2016
Publication Date Nov 3, 2016
Deposit Date Dec 2, 2016
Publicly Available Date Dec 2, 2016
Journal Cell
Print ISSN 0092-8674
Electronic ISSN 1097-4172
Publisher Elsevier (Cell Press)
Peer Reviewed Peer Reviewed
Volume 167
Issue 4
Article Number 1079-1087.e5
Pages 1079-1087.e5
DOI https://doi.org/10.1016/j.cell.2016.10.013
Keywords Ebola virus; Makona; pseudovirus; tropism; human; bat; adaptation; evolution; epistasis
Public URL http://eprints.nottingham.ac.uk/id/eprint/39138
Publisher URL http://www.sciencedirect.com/science/article/pii/S0092867416313964
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0
Additional Information This article is maintained by: Elsevier; Article Title: Human Adaptation of Ebola Virus during the West African Outbreak; Journal Title: Cell; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.cell.2016.10.013; CrossRef DOI link to the associated document: https://doi.org/10.1016/j.cell.2016.10.014; Content Type: article; Copyright: © 2016 The Authors. Published by Elsevier Inc.

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0





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