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Cell. 2016 Nov 3;167(4):1088-1098.e6. doi: 10.1016/j.cell.2016.10.014.

Ebola Virus Glycoprotein with Increased Infectivity Dominated the 2013-2016 Epidemic.

Author information

1
Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Worcester, MA 01605, USA.
2
Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA; Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA.
3
Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
4
Institute of Evolutionary Biology, University of Edinburgh, Ashworth Laboratories, Kings Buildings, West Mains Road, Edinburgh EH9 3JT, Scotland, UK.
5
Department of Medicine, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01605, USA.
6
Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Worcester, MA 01605, USA; Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
7
Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA; Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA; Scripps Translational Science Institute, 3344 North Torrey Pines Court, La Jolla, CA 92037, USA. Electronic address: andersen@scripps.edu.
8
Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA; Harvard University, 52 Oxford Street, Cambridge, MA 02138, USA. Electronic address: pardis@broadinstitute.org.
9
Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Worcester, MA 01605, USA. Electronic address: jeremy.luban@umassmed.edu.

Abstract

The magnitude of the 2013-2016 Ebola virus disease (EVD) epidemic enabled an unprecedented number of viral mutations to occur over successive human-to-human transmission events, increasing the probability that adaptation to the human host occurred during the outbreak. We investigated one nonsynonymous mutation, Ebola virus (EBOV) glycoprotein (GP) mutant A82V, for its effect on viral infectivity. This mutation, located at the NPC1-binding site on EBOV GP, occurred early in the 2013-2016 outbreak and rose to high frequency. We found that GP-A82V had heightened ability to infect primate cells, including human dendritic cells. The increased infectivity was restricted to cells that have primate-specific NPC1 sequences at the EBOV interface, suggesting that this mutation was indeed an adaptation to the human host. GP-A82V was associated with increased mortality, consistent with the hypothesis that the heightened intrinsic infectivity of GP-A82V contributed to disease severity during the EVD epidemic.

KEYWORDS:

Ebola virus; Filovirus; NPC1; RNA virus; adaptation; epidemic; glycoprotein; infection; mutation; outbreak

PMID:
27814506
PMCID:
PMC5115602
DOI:
10.1016/j.cell.2016.10.014
[Indexed for MEDLINE]
Free PMC Article

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