@article{9bd24ad9d04d4f558c337078682de921,
title = "Human Adaptation of Ebola Virus during the West African Outbreak",
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 co-circulation 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.",
keywords = "Ebola virus, Makona, adaptation, bat, epistasis, evolution, human, pseudovirus, tropism",
author = "Urbanowicz, {Richard A.} and McClure, {C. Patrick} and Anavaj Sakuntabhai and Sall, {Amadou A.} and Gary Kobinger and M{\"u}ller, {Marcel A.} and Holmes, {Edward C.} and Rey, {F{\'e}lix A.} and Etienne Simon-Loriere and Ball, {Jonathan K.}",
note = "Funding Information: This study was supported by funding from the Medical Research Council (G0801169), the Biotechnology and Biological Sciences Research Council (BB/M018636/1), the French Government{\textquoteright}s Investissement d{\textquoteright}Avenir program, Laboratoire d{\textquoteright}Excellence “Integrative Biology of Emerging Infectious Diseases” (grant n°ANR-10-LABX-62-IBEID), the Institut Pasteur Ebola Task Force, and the University of Nottingham Faculty of Medicine and Health Sciences International Research Collaboration Fund. E.C.H. is supported by an NHMRC Australia fellowship (AF30). Bat cells were generated within the framework of EU-FP7 ANTIGONE (no. 278976) and the EBOKON project supported by the Federal Ministry of Education and Research (BMBF). The authors would like to thank Prof. Greg Towers of University College London for discussions about host lentiviral restriction factors and Andrew Rambaut of University of Edinburgh for the sequence alignment dataset (see Key Resources Table ). Publisher Copyright: {\textcopyright} 2016 The Authors",
year = "2016",
month = nov,
day = "3",
doi = "10.1016/j.cell.2016.10.013",
language = "English (US)",
volume = "167",
pages = "1079--1087.e5",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "4",
}