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.