A Mouse Model for Evaluation of Prophylaxis and Therapy of Ebola Hemorrhagic Fever

• Published in: The Journal of infectious diseases Vol. 178; no. 3; pp. 651 - 661
• Main Authors: Bray, Mike, Davis, Kelly, Geisbert, Tom, Schmaljohn, Connie, Huggins, John
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 01-09-1998; University of Chicago Press; Oxford University Press
• Subjects: Animals; Antibodies, Viral - immunology; Biological and medical sciences; Cercopithecus aethiops; Disease Models, Animal; Diseases; Ebola virus; Ebola virus zaire; Ebolavirus - immunology; Ebolavirus - pathogenicity; Evaluation Studies as Topic; Experimental viral diseases and models; Hemorrhagic Fever, Ebola - immunology; Hemorrhagic Fever, Ebola - prevention & control; Hemorrhagic Fever, Ebola - virology; Immunization; Immunoenzyme Techniques; Infections; Infectious diseases; Inoculation; Lethal dose 50; Liver; Liver - pathology; Major Articles; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Neutralization Tests; Spleen; Spleen - pathology; Vero Cells; Viral diseases; Viral Envelope Proteins - genetics; Virions; Viruses; Performance evaluation; Animal model; Rodentia; Ebola hemorrhagic fever; Infection; Virus; Ebola virus; Mononegavirales; Vertebrata; Mammalia; Mouse; Filoviridae; Serotype specificity; Viral disease; Filovirus
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/515386

The Zaire subtype of Ebola virus (EBO-Z) is lethal for newborn mice, but adult mice are resistant to the virus, which prevents their use as an animal model of lethal Ebola infection. We serially passed EBO-Z virus in progressively older suckling mice, eventually obtaining a plaque-purified virus that was lethal for mature, immunocompetent BALB/c and C57BL/6 inbred and ICR (CD-1) outbred mice. Pathologic changes in the liver and spleen of infected mice resembled those in EBO-Z-infected primates. Virus titers in these tissues reached 109 pfu/g. The LD50 of mouse-adapted EBO-Z virus inoculated into the peritoneal cavity was ∼1 virion. Mice were resistant to large doses of the same virus inoculated subcutaneously, intradermally, or intramuscularly. Mice injected peripherally with mouse-adapted or intraperitoneally with non-adapted EBO-Z virus resisted subsequent challenge with mouse-adapted virus.