A Mouse Model of Zika Virus Pathogenesis.
A Mouse Model of Zika Virus Pathogenesis.
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DOI：
10.1016/j.chom.2016.03.010
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发表时间：
2016-05-11
影响因子：
30.3
通讯作者：
Diamond MS
中科院分区：
文献类型：
--
作者：
Lazear HM;Govero J;Smith AM;Platt DJ;Fernandez E;Miner JJ;Diamond MS
由于寨卡病毒（ZIKV）的持续流行和意想不到的临床结果，包括格林-巴利综合征和出生缺陷，迫切需要开发动物模型。我们评估了当代和历史ZIKV毒株在免疫活性小鼠和缺乏先天抗病毒应答组分的转基因小鼠中的感染和发病机制。尽管4至6周龄的野生型、Irf 3 −/−、Irf 5 −/−和Mavs−/−小鼠没有表现出明显的临床疾病，但Irf 3 −/− Irf 5 −/− Irf 7 −/− TKO和Ifnar 1 −/−小鼠出现神经系统疾病并死于ZIKV感染。Ifnar 1 −/−小鼠在大脑和脊髓中持续高病毒载量，这与ZIKV导致人类胎儿神经发育缺陷的证据一致。在Ifnar 1 −/−小鼠的睾丸中检测到最高的病毒载量，这与ZIKV的性传播有关。ZIKV发病机制的这种模型对于评估疫苗和治疗剂以及理解疾病发病机制和免疫逃避的基本机制将是有价值的。
Due to the ongoing Zika virus (ZIKV) epidemic and unexpected clinical outcomes including Guillain-Barré syndrome and birth defects, there is an urgent need for animal model development. We evaluated infection and pathogenesis with contemporary and historical ZIKV strains in immunocompetent mice and transgenic mice lacking components of the innate antiviral response. Whereas 4 to 6 week-old wild-type, Irf3−/−, Irf5−/−, and Mavs−/−, mice showed no overt clinical illness, Irf3−/− Irf5−/− Irf7−/− TKO and Ifnar1−/− mice developed neurological disease and succumbed to ZIKV infection. Ifnar1−/− mice sustained high viral loads in the brain and spinal cord, consistent with evidence that ZIKV causes neurodevelopmental defects in human fetuses. The highest viral loads were detected in the testes of Ifnar1−/− mice, which is relevant to sexual transmission of ZIKV. This model of ZIKV pathogenesis will be valuable for evaluating vaccines and therapeutics, as well as understanding basic mechanisms of disease pathogenesis and immune evasion.