Characterization of a Novel Murine Model to Study Zika Virus.
Characterization of a Novel Murine Model to Study Zika Virus.
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DOI：
10.4269/ajtmh.16-0111
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发表时间：
2016-06-01
期刊：
影响因子：
--
通讯作者：
Weaver SC
中科院分区：
文献类型：
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作者：
Rossi SL;Tesh RB;Azar SR;Muruato AE;Hanley KA;Auguste AJ;Langsjoen RM;Paessler S;Vasilakis N;Weaver SC
蚊媒寨卡病毒(ZIKV)是整个美洲持续爆发的发热性疾病的罪魁祸首。ZIKV以前被认为只会引起一种轻微的流感样疾病，但在当前的疫情中，发现与格林-巴利综合征和新生儿小头畸形有关。先前的一项研究表明，ZIKV需要小鼠适应才能产生可复制的小鼠疾病。在我们的研究中，一种低传代柬埔寨分离株以年龄依赖的方式在缺乏干扰素(干扰素)α受体的小鼠(A129小鼠)中引起疾病和死亡，但在类似年龄的免疫能力小鼠中没有。在A129小鼠中，病毒血症在感染后第2天达到高峰，∼107空斑形成单位/毫升，在第1天在脾中达到高滴度。在第3天在大脑中检测到ZIKV，并在第6天引起包括震颤在内的神经系统疾病的迹象。在睾丸中也发现了强劲的复制。在这个模型中，所有在最小年龄(3周)感染的小鼠在第7天死于疾病。年龄较大的小鼠(11周)出现了疾病、病毒血症和体重减轻的迹象，但从第8天开始恢复。此外，缺乏I型和II型干扰素反应的AG129小鼠支持与A129小鼠相似的感染动力学，但疾病体征被夸大了。这种在小鼠模型中对亚洲血统ZIKV毒株的表征，以及为数不多的报告寨卡病毒疾病模型并证明与年龄相关的发病率和死亡率的研究之一，可以为测试抗病毒药物和疫苗的有效性提供一个平台。
The mosquito-borne Zika virus (ZIKV) is responsible for an explosive ongoing outbreak of febrile illness across the Americas. ZIKV was previously thought to cause only a mild, flu-like illness, but during the current outbreak, an association with Guillain–Barré syndrome and microcephaly in neonates has been detected. A previous study showed that ZIKV requires murine adaptation to generate reproducible murine disease. In our study, a low-passage Cambodian isolate caused disease and mortality in mice lacking the interferon (IFN) alpha receptor (A129 mice) in an age-dependent manner, but not in similarly aged immunocompetent mice. In A129 mice, viremia peaked at ∼107 plaque-forming units/mL by day 2 postinfection (PI) and reached high titers in the spleen by day 1. ZIKV was detected in the brain on day 3 PI and caused signs of neurologic disease, including tremors, by day 6. Robust replication was also noted in the testis. In this model, all mice infected at the youngest age (3 weeks) succumbed to illness by day 7 PI. Older mice (11 weeks) showed signs of illness, viremia, and weight loss but recovered starting on day 8. In addition, AG129 mice, which lack both type I and II IFN responses, supported similar infection kinetics to A129 mice, but with exaggerated disease signs. This characterization of an Asian lineage ZIKV strain in a murine model, and one of the few studies reporting a model of Zika disease and demonstrating age-dependent morbidity and mortality, could provide a platform for testing the efficacy of antivirals and vaccines.