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Literature detail

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].
PMID 27814505 2016 Cell eng ppublish
PubMed DOI Browse context

Article

Publication summary

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.

adaptation bat Ebola virus epistasis evolution human Makona pseudovirus tropism Biological Evolution Host Specificity Africa, Western Animals Chiroptera Disease Outbreaks Ebolavirus Hemorrhagic Fever, Ebola Humans

Structured evidence records

Evidence records

5 total
Host Range Experiment 2 records
Host Range Experiment Extraction confidence 0.90
Key finding

Ebola virus pseudoviruses carrying lineage-defining GP mutations showed increased infectivity for human cells and reduced infectivity for bat cells.

Virus
EBOV
Location
Not specified
Supporting text

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.

Method
pseudovirus infection assay
Experimental system
pseudovirus assay
Host Range Experiment Extraction confidence 0.90
Key finding

Ebola virus pseudoviruses carrying lineage-defining GP mutations showed reduced infectivity for bat cells compared with human cells.

Virus
EBOV
Location
Not specified
Supporting text

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.

Method
pseudovirus infection assay
Experimental system
pseudovirus assay
Genomic Evolution 1 records
Genomic Evolution Extraction confidence 0.80
Key finding

Genomic and phylogenetic analyses identified amino acid substitutions in the Ebola virus glycoprotein that arose during the West African outbreak, enhancing infectivity for human cells and reducing tropism for bat cells.

Virus
EBOV
Location
Not specified
Supporting text

Phylogenetic analysis revealed the co-circulation of several viral lineages. We generated a synthetic glycoprotein (GP) construct based on the earliest reported isolate and introduced amino acid substitutions that defined viral lineages. 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
glycoprotein (GP)
Analysis methods
phylogenetic analysis; comparative genomics
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.95
Key finding

Amino acid substitutions in the Ebola virus glycoprotein enhanced infectivity and tropism for human cells relative to bat cells, indicating host adaptation during the West African outbreak.

Virus
EBOV
Host
Not specified
Location
Not specified
Supporting text

Specific amino acid substitutions in the EBOV GP have increased tropism for human cells, while reducing tropism for bat cells.

Genes or proteins
glycoprotein; GP
Mechanism types
tissue_tropism; host_adaptation; pathogenicity
Spillover Event 1 records
Spillover Event Extraction confidence 0.95
Key finding

Ebola virus spilled over from an animal reservoir, most likely bats, into humans at the start of the 2013–2016 West African outbreak.

Virus
EBOV
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
outbreak investigation
Transmission direction
animal-to-human
Geographic raw
West Africa