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

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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, Haddock, Elaine, LaCasse, Rachel, Thomas, Matthew J., Sova, Pavel, Carter, Victoria S., Weiss, Jeffrey M., Miller, Darla R., Shaw, Ginger D., Korth, Marcus J., Heise, Mark T., Baric, Ralph S., de Villena, Fernando Pardo-Manuel, Feldmann, Heinz, Katze, Michael G.·2014·Science

DOI 10.1126/science.1259595PMC PMC4241145

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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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Additional file 6 of Using the collaborative cross to identify the role of host genetics in defining the murine gut microbiome
Nagarajan, A., Scoggin, K., Gupta, J., Threadgill, D. W., & Andrews‐Polymenis, H. L. (2024) · Figshare · doi:10.6084/m9.figshare.26602993
Additional file 2 of Using the collaborative cross to identify the role of host genetics in defining the murine gut microbiome
Nagarajan, A., Scoggin, K., Gupta, J., Threadgill, D. W., & Andrews‐Polymenis, H. L. (2023) · Figshare · doi:10.6084/m9.figshare.26602981
Additional file 2 of Collaborative cross strain CC011/UncJ as a novel mouse model of T2-high, severe asthma
Donoghue, L. J., McFadden, K. M., Vargas, D., Smith, G. J., Immormino, R. M., Moran, T. P., & Kelada, S. N. P. (2023) · Figshare · doi:10.6084/m9.figshare.23488817
Additional file 13 of Using the collaborative cross to identify the role of host genetics in defining the murine gut microbiome
Nagarajan, A., Scoggin, K., Gupta, J., Threadgill, D. W., & Andrews‐Polymenis, H. L. (2024) · Figshare · doi:10.6084/m9.figshare.26603014
Additional file 10 of Using the collaborative cross to identify the role of host genetics in defining the murine gut microbiome
Nagarajan, A., Scoggin, K., Gupta, J., Threadgill, D. W., & Andrews‐Polymenis, H. L. (2024) · Figshare · doi:10.6084/m9.figshare.26603005
Additional file 7 of Using the collaborative cross to identify the role of host genetics in defining the murine gut microbiome
Nagarajan, A., Scoggin, K., Gupta, J., Threadgill, D. W., & Andrews‐Polymenis, H. L. (2024) · Figshare · doi:10.6084/m9.figshare.26602996
Additional file 1 of Using the collaborative cross to identify the role of host genetics in defining the murine gut microbiome
Nagarajan, A., Scoggin, K., Gupta, J., Threadgill, D. W., & Andrews‐Polymenis, H. L. (2023) · Figshare · doi:10.6084/m9.figshare.26602978
Additional file 5 of Using the collaborative cross to identify the role of host genetics in defining the murine gut microbiome
Nagarajan, A., Scoggin, K., Gupta, J., Threadgill, D. W., & Andrews‐Polymenis, H. L. (2024) · Figshare · doi:10.6084/m9.figshare.26602990
Additional file 3 of Using the collaborative cross to identify the role of host genetics in defining the murine gut microbiome
Nagarajan, A., Scoggin, K., Gupta, J., Threadgill, D. W., & Andrews‐Polymenis, H. L. (2023) · Figshare · doi:10.6084/m9.figshare.26602984
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Liabotis, A. (2018) · theses.fr (ABES) · doi:10.70675/52bcdc87z9aedz40abz9459z9019f91b56fe
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Danet, N. (2019) · theses.fr (ABES) · doi:10.70675/d7320788zd527z4fc7z8d6bzff30bb902d07
Ebola Virus Disease, Vaccines, Therapeutics, Transmission, and Long-Term Sequelae: Scoping Review with ☸SAIMSARA
SAIMSARA (2026) · SAIMSARA Journal · doi:10.62487/saimsara976931fc
Editor’s Note for the Report “Host genetic diversity enables Ebola hemorrhagic fever pathogenesis and resistance”
Thorp, H. H. (2026) · Science · doi:10.1126/science.aek4288
Systems genetics analysis reveals immune mediators of coronavirus disease severity in mice
Risemberg, E. L., Leist, S. R., Schäfer, A., Kamat, K., Bell, T. A., Hock, P., Jensen, K., Linnertz, C. L., Miller, D. R., Shaw, G. D., et al. (2026) · Genetics · doi:10.1093/genetics/iyag209
Self-citation
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Zohud, O., Nashef, A., Elnaaj, A., & Iraqi, F. A. (2026) · Animal Models and Experimental Medicine · doi:10.1002/ame2.70283
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Jordan, R., Archin, N. M., Barclay, W., Brancale, A., Cagno, V., Cardin, R. D., Carter, K. L., Delang, L., Rocha‐Pereira, J., Feng, J. Y., et al. (2026) · Antiviral Research · doi:10.1016/j.antiviral.2026.106549

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.
ORCID: Rasmussen, Angela L.
Okumura, Atsushi
Ferris, Martin T.
Green, Richard
Feldmann, Friederike
Scott, Dana P.
Safronetz, David
Haddock, Elaine
Thomas, Matthew J.
Weiss, Jeffrey M.
Miller, Darla R.
Shaw, Ginger D.
Korth, Marcus J.
Heise, Mark T.
Baric, Ralph S.
Feldmann, Heinz
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2014-11-21
Volume: 346
Issue: 6212
Pages: 987-991
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.1259595
PMC: PMC4241145
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: green
www.ncbi.nlm.nih.gov
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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Host genetic diversity enables Ebola hemorrhagic fever pathogenesis and resistance

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