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

Authors

• Mike Bray, Divisions of Virology and Pathology, US Army Medical ResearchFollow
• Kelly Davis, Divisions of Virology and Pathology, US Army Medical Research
• Tom Geisbert, Divisions of Virology and Pathology, US Army Medical Research
• Connie Schmaljohn, Institute of Infectious Diseases, Fort Detrick, Frederick, MarylandFollow
• John Higgins, Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland

Document Type

Article

Date of this Version

1998

Citation

The Journal of Infectious Diseases 1998;178:651–61

Comments

This article is a U.S. government work, and is not subject to copyright in the United States.

Abstract

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 EBOZ– 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.