OmniVira

Human Adaptation of Ebola Virus during the West African Outbreak.

Richard A Urbanowicz1,2 C Patrick McClure1,2 Anavaj Sakuntabhai3,4 Amadou A Sall5 Gary Kobinger6,7,8 Marcel A Müller9 Edward C Holmes10 Félix A Rey11,12 Etienne Simon-Loriere3,13 Jonathan K Ball1,14
Affiliations 14 institutions
  1. School of Life Sciences, The University of Nottingham, Nottingham NG7 2RD, UK
  2. NIHR Nottingham Digestive Diseases Biomedical Research Unit, The University of Nottingham, Nottingham University Hospitals NHS Trust, Nottingham NG7 2UH, UK.
  3. Functional Genetics of Infectious Diseases Unit, Institut Pasteur, 75724 Paris Cedex 15, France
  4. Centre National de la Recherche Scientifique, Unité de Recherche Associée 3012, 75015 Paris, France.
  5. Arbovirus and Viral Hemorrhagic Fever Unit, Institut Pasteur de Dakar, BP 220 Dakar, Senegal.
  6. Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Ottawa, ON K1A 0K9, Canada
  7. Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3R2, Canada
  8. Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Winnipeg, MB R32T 2N2, Canada.
  9. Institute of Virology, University of Bonn Medical Center, 53127 Bonn, Germany.
  10. 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.
  11. Institut Pasteur, Département de Virologie, Unité de Virologie Structurale, 75724 Paris Cedex 15, France
  12. Centre National de la Recherche Scientifique, Unité Mixte de Recherche 3569, 75724 Paris Cedex 15, France.
  13. Centre National de la Recherche Scientifique, Unité de Recherche Associée 3012, 75015 Paris, France. Electronic address: [email protected].
  14. NIHR Nottingham Digestive Diseases Biomedical Research Unit, The University of Nottingham, Nottingham University Hospitals NHS Trust, Nottingham NG7 2UH, UK. Electronic address: [email protected].
PMID27814505 DOI10.1016/j.cell.2016.10.013 Year2016 Journal Cell Languageeng Statusppublish

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.

Supporting text Virus Host Location
adaptation 13 bat 54 Ebola virus 18 epistasis 1 evolution 62 human 14 Makona 1 pseudovirus 4 tropism 16 Biological Evolution 28 Host Specificity 132 Africa, Western 6 Animals 1948 Chiroptera 371 Disease Outbreaks 170 Ebolavirus 31 Hemorrhagic Fever, Ebola 27 Humans 1440 Mutation 209 Phylogeny 805 Viral Envelope Proteins 60 Zoonoses 397 envelope glycoprotein, Ebola virus 4

Evidence records

3 total
Transmission Evidence
1 records · 1 evidence types
Evidence type Spillover Event
1 records
OVE2456 Spillover Event
Key finding

The 2013–2016 Ebola outbreak began after cross-species transmission of EBOV from bats into humans in West Africa.

Virus
Ebola virus
Host
human Homo sapiens Natural host bats Chiroptera Natural host
Location
West Africa
Supporting text

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.

Method
phylogenetic analysis
Study design
epidemiological inference of outbreak origin
Transmission direction
animal-to-human
Geographic raw
West Africa
Functional Mechanism
1 records · 1 evidence types
Evidence type Molecular Adaptation
1 records
OVE2459 Molecular Adaptation
Key finding

Amino acid substitutions in Ebola virus glycoprotein increased tropism for human cells and reduced tropism for bat cells, indicating viral adaptation to human hosts.

Virus
Ebola virus
Host
Not specified
Location
Not specified
Supporting text

These data revealed that specific amino acid substitutions in the EBOV GP have increased tropism for human cells, while reducing tropism for bat cells.

Genes or proteins
GP
Mechanism types
tissue tropism | host-range expansion | transmission fitness
Genomic Evolution
1 records · 1 evidence types
Evidence type Phylogenetic Evolution
1 records
OVE2457 Phylogenetic Evolution
Key finding

Phylogenetic analysis showed that several Ebola virus (EBOV) lineages co-circulated during the West African outbreak.

Virus
Ebola virus
Host
human Homo sapiens Natural host
Location
Not specified
Supporting text

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.

Analysis methods
phylogenetic analysis