Susceptibility and Lethality of Western Equine Encephalitis Virus in Balb/c Mice When Infected by the Aerosol Route
Susceptibility and Lethality of Western Equine Encephalitis Virus in Balb/c Mice When Infected by the Aerosol Route
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DOI：
10.3390/v9070163
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发表时间：
2017-07-01
期刊：
影响因子：
4.7
通讯作者：
Ulaeto, David O.
中科院分区：
文献类型：
--
作者：
Phelps, Amanda L.;O'Brien, Lyn M.;Ulaeto, David O.
西方马脑炎病毒（WEEV）在蚊子和鸟类或啮齿动物之间自然循环，在动物流行病爆发期间，人类的病死率高达15%。没有治疗WEEV感染的医学对策，意外的气溶胶暴露使病死率增加到40%。了解感染的发病机制是制定和评估医疗对策的必要条件。本研究描述了通过气溶胶途径感染WEEV的小鼠的临床和病理学结果，并用作人类WEEV感染的模型。Balb/c小鼠通过气溶胶途径感染高毒力WEEV Fleming株的剂量范围，以确定半数致死量（MLD）。该疾病的过程是急性的，最终严重的临床体征，神经浸润，和剂量依赖性死亡率。通过气溶胶途径对另外几组小鼠进行暴露，定期处死，并切除组织进行组织病理学检查和病毒学检查。病毒滴度在脑和肺中在攻毒后4天达到峰值，对应于脑吻腹侧区域的严重双侧病变，尤其是嗅球和梨状皮质。重述人类WEEV疾病在小鼠中的最严重的临床表现可能证明是一个有用的工具，在评估医疗对策。
Western equine encephalitis virus (WEEV) naturally cycles between mosquitos and birds or rodents, with a case fatality rate of up to 15% in humans during epizootic outbreaks. There are no medical countermeasures to treat WEEV infection, and accidental aerosol exposure increases the case fatality rate up to 40%. Understanding the pathogenesis of infection is required to develop and assess medical countermeasures. This study describes the clinical and pathological findings of mice infected with WEEV by the aerosol route, and use as a model for WEEV infection in humans. Balb/c mice were infected by the aerosol route with a dose range of high-virulence WEEV strain Fleming to establish the median lethal dose (MLD). The disease course was acute, culminating in severe clinical signs, neuroinvasion, and dose-dependent mortality. Further groups of mice were exposed by the aerosol route, periodically sacrificed, and tissues excised for histopathological examination and virology. Viral titres peaked four days post-challenge in the brain and lungs, corresponding with severe bilateral lesions in rostroventral regions of the encephalon, especially in the olfactory bulb and piriform cortex. Recapitulation of the most serious clinical presentations of human WEEV disease in mice may prove a useful tool in the evaluation of medical countermeasures.