Cited by 301Viral Infections and Outbreaks ResearchViral Infections and VectorsVirology and Viral Diseases

Host genetic diversity enables Ebola hemorrhagic fever pathogenesis and resistance

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Rasmussen, Angela L., Okumura, Atsushi, Ferris, Martin T., Green, Richard, Feldmann, Friederike, Kelly, Sara M., Scott, Dana P., Safronetz, David +14 more·2014·Science

Abstract

Existing mouse models of lethal Ebola virus infection do not reproduce hallmark symptoms of Ebola hemorrhagic fever, neither delayed blood coagulation and disseminated intravascular coagulation nor death from shock, thus restricting pathogenesis studies to nonhuman primates. Here we show that mice from the Collaborative Cross panel of recombinant inbred mice exhibit distinct disease phenotypes after mouse-adapted Ebola virus infection. Phenotypes range from complete resistance to lethal disease to severe hemorrhagic fever characterized by prolonged coagulation times and 100% mortality. Inflammatory signaling was associated with vascular permeability and endothelial activation, and resistance to lethal infection arose by induction of lymphocyte differentiation and cellular adhesion, probably mediated by the susceptibility allele Tek . These data indicate that genetic background determines susceptibility to Ebola hemorrhagic fever.

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  • Reduced Tie2 expression is associated with susceptibility to vascular complications induced by haemorrhagic Ebola virus infection in mice.

    “Furthermore, reduced Tie2 expression was recently associated with susceptibility to vascular complications induced by haemorrhagic Ebola virus infection in mice50.”

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Authors
Rasmussen, A. L., Okumura, A., Ferris, M. T., Green, R., Feldmann, F., Kelly, S. M., Scott, D. P., Safronetz, D., Haddock, E., LaCasse, R., Thomas, M. J., Sova, P., Carter, V. S., Weiss, J. M., Miller, D. R., Shaw, G. D., Korth, M. J., Heise, M. T., Baric, R. S., de Villena, F. P.-M., Feldmann, H., & Katze, M. G.
Affiliations
  • University of Washington (US)
  • National Institutes of Health (US)
  • University of North Carolina at Chapel Hill (US)
  • Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
Corresponding author
  • Rasmussen, Angela L.
  • Okumura, Atsushi
  • Katze, Michael G.
Venue
Science
Published
2014-11-21
Volume
346
Issue
6212
Pages
987-991
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W1986492410
Cited by
290
References
28
Citations by year
2026: 5 · 2025: 7 · 2024: 19 · 2023: 23 · 2022: 22 · 2021: 22 · 2020: 13 · 2019: 27 · 2018: 24 · 2017: 39 · 2016: 44 · 2015: 34 · 2014: 11
FWCI
29.89
Type
journal article
Language
en
Open access
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
  • UNC Libraries
Funders
  • National Institutes of Health (P51OD010425)
  • National Institute of Allergy and Infectious Diseases (U54AI081680, U19AI100625, U19AI109761)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Viral Infections and Outbreaks Research
  • Health Sciences › Medicine › Infectious Diseases › Viral Infections and Vectors
  • Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
Keywords
Ebola virus, hemorrhagic fever, host genetic variation, Collaborative Cross mice, recombinant inbred mouse strains, disease susceptibility, disseminated intravascular coagulation, coagulation, shock, lymphocyte differentiation, endothelial activation, vascular permeability, inflammatory signaling
MeSH terms
Alleles, Animals, Blood Coagulation, Capillary Permeability, Disease Models, Animal, Endothelium, Vascular, Liver, Lymphocyte Activation, Mice, Inbred C57BL, Neovascularization, Physiologic, Hemorrhagic Fever, Ebola, Genetic Predisposition to Disease, Receptor, TIE-2, Mice, Host-Pathogen Interactions

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