Type I interferon induction is correlated with attenuation of a South American eastern equine encephalitis virus strain in mice

Virology. 2009 Aug 1;390(2):338-47. doi: 10.1016/j.virol.2009.05.030. Epub 2009 Jun 18.


North American eastern equine encephalitis virus (NA-EEEV) strains cause high mortality in humans, whereas South American strains (SA-EEEV) are typically avirulent. To clarify mechanisms of SA-EEEV attenuation, we compared mouse-attenuated BeAr436087 SA-EEEV, considered an EEEV vaccine candidate, with mouse-virulent NA-EEEV strain, FL93-939. Although attenuated, BeAr436087 initially replicated more efficiently than FL93-939 in lymphoid and other tissues, inducing systemic IFN-alpha/beta release, whereas FL93-939 induced little. BeAr436087 was more virulent than FL93-939 in IFN-alpha/beta-deficient mice, confirming that type I IFN responses determined attenuation, but the viruses were similarly sensitive to IFN-alpha/beta priming in vitro. Infection with BeAr436087 protected against FL93-939 disease/death, even when given 8 h afterward, suggesting that the environment produced by BeAr436087 infection attenuated FL93-939. We conclude that avoidance of IFN-alpha/beta induction is a major virulence factor for FL93-939. Furthermore, BeAr436087 could be used for vaccination and therapeutic treatment in the event of exposure to NA-EEEV during a bioterrorism attack.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Encephalitis Virus, Eastern Equine / immunology*
  • Encephalitis Virus, Eastern Equine / pathogenicity*
  • Humans
  • Interferon-alpha / blood
  • Interferon-alpha / deficiency
  • Interferon-alpha / immunology*
  • Interferon-beta / blood
  • Interferon-beta / deficiency
  • Interferon-beta / immunology*
  • Mice
  • Mice, Knockout
  • Virulence


  • Interferon-alpha
  • Interferon-beta