Human Adaptation of Ebola Virus during the West African Outbreak

Urbanowicz, Richard A.; McClure, C. Patrick; Sakuntabhai, Anavaj; Sall, Amadou A.; Kobinger, Gary; M�ller, Marcel A.; Holmes, Edward C.; Rey, F�lix A.; Simon-Loriere, Etienne; Ball, Jonathan K.

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., Holmes, E. C., Rey, F. A., Simon-Loriere, E., & 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: 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: https://nottingham-repository.worktribe.com/output/830260
• Publisher URL: http://www.sciencedirect.com/science/article/pii/S0092867416313964
• 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.
• Contract Date: Dec 2, 2016