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, 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 10(9) pfu/g. The LD50 of mouse-adapted EBO-Z virus inoculated into the peritoneal cavity was approximately 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.
Bray
M
M
Division of Virology, US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland 21702-5011, USA. bray@ncifcrf.gov
Davis
K
K
Geisbert
T
T
Schmaljohn
C
C
Huggins
J
J
D000222:Adaptation, Physiological; D000818:Animals; D000831:Animals, Newborn; D000833:Animals, Suckling; D004195:Disease Models, Animal; D029043:Ebolavirus / Q000145:classification / Q000472:pathogenicity / Q000502:physiology; D005260:Female; D019142:Hemorrhagic Fever, Ebola / Q000209:etiology* / Q000517:prevention & control / Q000628:therapy; D007114:Immunization; D008099:Liver / Q000473:pathology / Q000821:virology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008854:Microscopy, Electron; D013154:Spleen / Q000473:pathology / Q000821:virology; D014774:Virulence; D014779:Virus Replication