Interferon α/β Receptor-Deficient Mice as a Model for Ebola Virus Disease

A major obstacle in ebolavirus research is the lack of a small-animal model for Sudan virus (SUDV), as well as other wild-type (WT) ebolaviruses. Here, we expand on research by Bray and by Lever et al suggesting that WT ebolaviruses are pathogenic in mice deficient for the type 1 interferon (IFN) α/...

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Bibliographic Details
Published in:The Journal of infectious diseases 2015-10, Vol.212 (suppl 2), p.S282-S294
Main Authors: Brannan, Jennifer M., Froude, Jeffery W., Prugar, Laura I., Bakken, Russell R., Zak, Samantha E., Daye, Sharon P., Wilheimsen, Catherine E., Dye, John M.
Format: Article
Language:English
Subjects:
Animals
Antibodies, Viral - immunology
Cell Line
Cercopithecus aethiops
Disease Models, Animal
Ebola Vaccines - immunology
Ebola virus
Ebolavirus
Ebolavirus - metabolism
Ebolavirus - pathogenicity
Glycoproteins - immunology
Glycoproteins - metabolism
Hemorrhagic Fever, Ebola - virology
Mice
Mice, Inbred C57BL
PATHOGENESIS
Receptor, Interferon alpha-beta - deficiency
Replicon - immunology
Vaccination - methods
Vero Cells - virology
Viral Proteins - immunology
Viral Proteins - metabolism
Virulence - immunology
Virulence - physiology
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Summary:A major obstacle in ebolavirus research is the lack of a small-animal model for Sudan virus (SUDV), as well as other wild-type (WT) ebolaviruses. Here, we expand on research by Bray and by Lever et al suggesting that WT ebolaviruses are pathogenic in mice deficient for the type 1 interferon (IFN) α/β receptor (IFNα/βR—/—). We examined the disease course of several WT ebolaviruses: Boneface (SUDV/Bon) and Gulu variants of SUDV, Ebola virus (EBOV), Bundibugyo virus (BDBV), Ta'i Forest virus, and Reston virus (RESTV). We determined that exposure to WT SUDV or EBOV results in reproducible signs of disease in IFNα/βR—/—mice, as measured by weight loss and partial lethality. Vaccination with the SUDV or EBOV glycoprotein (GP)-expressing Venezuelan equine encephalitis viral replicon particle vaccine protected these mice from SUDV/Bon and EBOV challenge, respectively. Treatment with SUDV-or EBOV-specific anti-GP antibodies protected mice from challenge when delivered 1-3 days after infection. Serial sampling experiments revealed evidence of disseminated intravascular coagulation in the livers of mice infected with the Boneface variant of SUDV, EBOV, and BDBV. Taken together, these data solidify the IFNα/βR—/— mouse as an important and useful model for the study of WT EBOV disease.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/jiv215