Protection from lethal infection is determined by innate immune responses in a mouse model of Ebola virus infection

Virology. 2003 Aug 1;312(2):415-24. doi: 10.1016/s0042-6822(03)00233-2.


A mouse-adapted strain of Ebola Zaire virus produces a fatal infection when BALB/cj mice are infected intraperitoneally (ip) but subcutaneous (sc) infection with the same virus fails to produce illness and confers long-term protection from lethal ip rechallenge. To identify immune correlates of protection in this model, we compared viral replication and cytokine/chemokine responses to Ebola virus in mice infected ip (10 PFU/mouse), or sc (100 PFU/mouse) and sc "immune" mice rechallenged ip (10(6) PFU/mouse) at several time points postinfection (pi). Ebola viral antigens were detected in the serum, liver, spleen, and kidneys of ip-infected mice by day 2 pi, increasing up to day 6. Sc-infected mice and immune mice rechallenged ip had no detectable viral antigens until day 6 pi, when low levels of viral antigens were detected in the livers of sc-infected mice only. TNF-alpha and MCP-1 were detected earlier and at significantly higher levels in the serum and tissues of ip-infected mice than in sc-infected or immune mice challenged ip. In contrast, high levels of IFN-alpha and IFN-gamma were found in tissues within 2 days after challenge in sc-infected and immune mice but not in ip-infected mice. Mice became resistant to ip challenge within 48 h of sc infection, coinciding with the rise in tissue IFN-alpha levels. In this model of Ebola virus infection, the nonlethal sc route of infection is associated with an attenuated inflammatory response and early production of antiviral cytokines, particularly IFN-alpha, as compared with lethal ip infection.

MeSH terms

  • Animals
  • Antigens, Viral / blood
  • Antigens, Viral / immunology
  • Disease Models, Animal*
  • Ebolavirus / growth & development
  • Ebolavirus / immunology*
  • Female
  • Hemorrhagic Fever, Ebola / immunology*
  • Hemorrhagic Fever, Ebola / prevention & control*
  • Immunity, Innate / immunology*
  • Inflammation / immunology
  • Kidney / immunology
  • Liver / immunology
  • Mice
  • Mice, Inbred BALB C
  • Spleen / immunology
  • Survival Rate


  • Antigens, Viral