A MOUSE MODEL FOR EVALUATION OF PROPHYLAXIS AND THERAPY OF EBOLA HEMORRHAGIC-FEVER

The Zaire subtype of Ebola virus (EBO-Z) is lethal for newborn mice, b ut adult mice are resistant to the virus, which prevents their use as an animal model of lethal Ebola infection. We serially passed EBO-Z vi rus in progressively older suckling mice, eventually obtaining a plaqu e-purified virus that was lethal for mature, immunocompetent BALB/c an d C57BL/6 inbred and ICR (CD-1) outbred mice. Pathologic changes in th e liver and spleen of infected mice resembled those in EBO-Z-infected primates. Virus titers in these tissues reached 10(9) pfu/g, The LD50 of mouse-adapted EBO-Z virus inoculated into the peritoneal cavity was similar to 1 virion, Mice were resistant to large doses of the same v irus inoculated subcutaneously, intradermally, or intramuscularly, Mic e injected peripherally with mouse-adapted or intraperitoneally with n on-adapted EBO-Z virus resisted subsequent challenge with mouse-adapte d virus.