Manipulation of host factors optimizes the pathogenesis of western equine encephalitis virus infections in mice for antiviral drug development.
Manipulation of host factors optimizes the pathogenesis of western equine encephalitis virus infections in mice for antiviral drug development.
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宿主因素的操纵优化了小鼠西方马脑炎病毒感染的发病机制，用于抗病毒药物的开发。
DOI：
10.1007/s13365-014-0297-8
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发表时间：
2015-02
影响因子：
3.2
通讯作者：
Irani, David N.
中科院分区：
文献类型：
--
作者：
Blakely, Pennelope K.;Delekta, Phillip C.;Miller, David J.;Irani, David N.
虽然甲病毒通过蚊子媒介自然传播，但有些也可以作为气溶胶传播，使其成为潜在的生物恐怖主义制剂。一种这样的病原体，西部马脑炎病毒（WEEV），通过多种感染途径并因此推测通过多种机制引起致命的人类脑炎。虽然WEEV也会在非人灵长类动物中产生急性脑炎，但重现人类疾病特征的小动物模型对于发病机制研究和评估候选抗病毒疗法都是有用的。我们已经优化了条件，感染小鼠与低传代分离的WEEV，从而允许详细调查病毒的嗜性，复制，神经侵袭，和神经毒力。我们发现，宿主因素强烈影响疾病的结果，特别是年龄，性别和遗传背景都有显着影响疾病的易感性独立的病毒嗜性或复制在中枢神经系统。我们的数据表明，实验变量可以在小鼠中进行调整，以概括已知在非人灵长类动物和人类中发生的疾病特征，从而有助于进一步研究WEEV的发病机制，并提供了一个现实的抗病毒药物输送的治疗窗口。
While alphaviruses spread naturally via mosquito vectors, some can also be transmitted as aerosols making them potential bioterrorism agents. One such pathogen, western equine encephalitis virus (WEEV), causes fatal human encephalitis via multiple routes of infection and thus presumably via multiple mechanisms. Although WEEV also produces acute encephalitis in non-human primates, a small animal model that recapitulates features of human disease would be useful for both pathogenesis studies and to evaluate candidate antiviral therapies. We have optimized conditions to infect mice with a low passage isolate of WEEV, thereby allowing detailed investigation of virus tropism, replication, neuroinvasion, and neurovirulence. We find that host factors strongly influence disease outcome, and in particular that age, gender and genetic background all have significant effects on disease susceptibility independent of virus tropism or replication within the central nervous system. Our data show that experimental variables can be adjusted in mice to recapitulate disease features known to occur in both non-human primates and humans, thus aiding further study of WEEV pathogenesis and providing a realistic therapeutic window for antiviral drug delivery.
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影响因子：
3.8
作者：
Nagata, Les P.;Hu, Wei-Gang;Wong, Jonathan P.
通讯作者：
Wong, Jonathan P.
影响因子：
3.7
作者：
Forrester, Naomi L.;Kenney, Joan L.;Weaver, Scott C.
通讯作者：
Weaver, Scott C.
影响因子：
3.7
作者：
Kimura, T;Griffin, DE
通讯作者：
Griffin, DE
影响因子：
11.2
作者：
Nargi-Aizenman, JL;Havert, MB;Griffin, DE
通讯作者：
Griffin, DE
影响因子：
3.3
作者：
Barna, M;Komatsu, T;Reiss, CS
通讯作者：
Reiss, CS