Human Adaptation of Ebola Virus during the West African Outbreak.
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.
School of Life Sciences, The University of Nottingham, Nottingham NG7 2RD, UK; NIHR Nottingham Digestive Diseases Biomedical Research Unit, The University of Nottingham, Nottingham University Hospitals NHS Trust, Nottingham NG7 2UH, UK.
Richard A
RA
Urbanowicz
School of Life Sciences, The University of Nottingham, Nottingham NG7 2RD, UK; NIHR Nottingham Digestive Diseases Biomedical Research Unit, The University of Nottingham, Nottingham University Hospitals NHS Trust, Nottingham NG7 2UH, UK.
C Patrick
CP
McClure
Functional Genetics of Infectious Diseases Unit, Institut Pasteur, 75724 Paris Cedex 15, France; Centre National de la Recherche Scientifique, Unité de Recherche Associée 3012, 75015 Paris, France.
Anavaj
A
Sakuntabhai
Arbovirus and Viral Hemorrhagic Fever Unit, Institut Pasteur de Dakar, BP 220 Dakar, Senegal.
Amadou A
AA
Sall
Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Ottawa, ON K1A 0K9, Canada; Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3R2, Canada; Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Winnipeg, MB R32T 2N2, Canada.
Gary
G
Kobinger
Institute of Virology, University of Bonn Medical Center, 53127 Bonn, Germany.
Marcel A
MA
Müller
Marie Bashir Institute for Infectious Diseases and Biosecurity, Charles Perkins Centre, School of Life and Environmental Sciences and Sydney Medical School, The University of Sydney, Sydney, NSW 2050, Australia.
Edward C
EC
Holmes
Institut Pasteur, Département de Virologie, Unité de Virologie Structurale, 75724 Paris Cedex 15, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 3569, 75724 Paris Cedex 15, France.
Félix A
FA
Rey
Functional Genetics of Infectious Diseases Unit, Institut Pasteur, 75724 Paris Cedex 15, France; Centre National de la Recherche Scientifique, Unité de Recherche Associée 3012, 75015 Paris, France. Electronic address: etienne.simon-loriere@pasteur.fr.
Etienne
E
Simon-Loriere
School of Life Sciences, The University of Nottingham, Nottingham NG7 2RD, UK; NIHR Nottingham Digestive Diseases Biomedical Research Unit, The University of Nottingham, Nottingham University Hospitals NHS Trust, Nottingham NG7 2UH, UK. Electronic address: jonathan.ball@nottingham.ac.uk.
Jonathan K
JK
Ball
D000354:Africa, Western / Q000453:epidemiology; D000818:Animals; D005075:Biological Evolution; D002685:Chiroptera / Q000821:virology; D004196:Disease Outbreaks; D029043:Ebolavirus / Q000145:classification / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D019142:Hemorrhagic Fever, Ebola / Q000453:epidemiology / Q000635:transmission / Q000821:virology*; D058507:Host Specificity; D006801:Humans; D009154:Mutation; D010802:Phylogeny; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism; D015047:Zoonoses
D014759:Viral Envelope Proteins; C113189:envelope glycoprotein, Ebola virus
Ebola virus; Makona; adaptation; bat; epistasis; evolution; human; pseudovirus; tropism