A mouse model for evaluation of prophylaxis and therapy of Ebola hemorrhagic fever

J Infect Dis. 1999 Feb;179 Suppl 1:S248-58. doi: 10.1086/514292.

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 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.

MeSH terms

  • Adaptation, Physiological
  • Animals
  • Animals, Newborn
  • Animals, Suckling
  • Disease Models, Animal
  • Ebolavirus / classification
  • Ebolavirus / pathogenicity
  • Ebolavirus / physiology
  • Female
  • Hemorrhagic Fever, Ebola / etiology*
  • Hemorrhagic Fever, Ebola / prevention & control
  • Hemorrhagic Fever, Ebola / therapy
  • Immunization
  • Liver / pathology
  • Liver / virology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred ICR
  • Microscopy, Electron
  • Spleen / pathology
  • Spleen / virology
  • Virulence
  • Virus Replication