Type I interferon induction is correlated with attenuation of a South American eastern equine encephalitis virus strain in mice.
Type I interferon induction is correlated with attenuation of a South American eastern equine encephalitis virus strain in mice.
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DOI：
10.1016/j.virol.2009.05.030
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发表时间：
2009-08-01
期刊：
影响因子：
3.7
通讯作者：
Ryman, Kate D.
中科院分区：
文献类型：
--
作者：
Gardner, Christina L.;Yin, Jun;Burke, Crystal W.;Klimstra, William B.;Ryman, Kate D.
北美东部马脑炎病毒（NA-EEEV）毒株在人类中引起高死亡率，而南美毒株（SA-EEEV）通常是无毒的。为了阐明SA-EEEV减毒的机制，我们比较了小鼠减毒BeAr 436087 SA-EEEV（被认为是EEEV疫苗候选者）与小鼠强毒NA-EEEV毒株FL 93 -939。尽管被减毒，BeAr 436087最初在淋巴和其他组织中比FL 93 -939更有效地复制，诱导全身IFN-α/β释放，而FL 93 -939诱导很少。在IFN-α/β缺陷小鼠中，BeAr 436087比FL 93 -939更具毒性，证实I型IFN应答决定减毒，但病毒对IFN-α/β体外引发的敏感性相似。用BeAr 436087感染保护了FL 93 -939疾病/死亡，即使在8小时后给予，这表明由BeAr 436087感染产生的环境使FL 93 -939减毒。我们得出结论，避免IFN-α/β诱导是FL 93 -939的因素。此外，BeAr 436087可用于在生物恐怖袭击期间暴露于NA-EEEV的情况下的疫苗接种和治疗性治疗。
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 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.
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DOI：
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发表时间：
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