Type I interferon induction is correlated with attenuation of a South American eastern equine encephalitis virus strain in mice.
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.
Gardner
Christina L
CL
Department of Microbiology and Immunology and Center for Molecular & Tumor Virology, Louisiana State University Health Sciences Center - Shreveport, 1501 Kings Highway, Shreveport, LA 71130-3932, USA.
Yin
Jun
J
Burke
Crystal W
CW
Klimstra
William B
WB
Ryman
Kate D
KD
D000818:Animals; D004663:Encephalitis Virus, Eastern Equine / Q000276:immunology* / Q000472:pathogenicity*; D006801:Humans; D016898:Interferon-alpha / Q000097:blood / Q000172:deficiency / Q000276:immunology*; D016899:Interferon-beta / Q000097:blood / Q000172:deficiency / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D014774:Virulence
D016898:Interferon-alpha; D016899:Interferon-beta