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

• Published in: Virology (New York, N.Y.) Vol. 390; no. 2; pp. 338 - 347
• Main Authors: Gardner, Christina L, Yin, Jun, Burke, Crystal W, Klimstra, William B, Ryman, Kate D
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2009
• Subjects: Alphavirus; animal disease models; Animals; Attenuation; Eastern equine encephalitis virus; Eastern equine encephalomyelitis; EEEV; Encephalitis Virus, Eastern Equine - immunology; Encephalitis Virus, Eastern Equine - pathogenicity; host-pathogen relationships; Humans; immune response; Infectious Disease; Interferon; Interferon-alpha - blood; Interferon-alpha - deficiency; Interferon-alpha - immunology; Interferon-beta - blood; Interferon-beta - deficiency; Interferon-beta - immunology; interferons; knockout mutants; live vaccines; Lymphoid tissue; Mice; Mice, Knockout; nonpathogenic strains; STAT1; vaccination; Virulence; virus replication; EEEV; Alphavirus; Attenuation; Interferon; Lymphoid tissue; STAT1
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2009.05.030

Abstract 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-α/β release, whereas FL93-939 induced little. BeAr436087 was more virulent than FL93-939 in IFN-α/β-deficient mice, confirming that type I IFN responses determined attenuation, but the viruses were similarly sensitive to IFN-α/β 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-α/β 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.