Zika Virus Fatally Infects Wild Type Neonatal Mice and Replicates in Central Nervous System.
Zika Virus Fatally Infects Wild Type Neonatal Mice and Replicates in Central Nervous System.
复制标题
DOI：
10.3390/v10010049
复制
发表时间：
2018-01-22
期刊：
影响因子：
--
通讯作者：
Tang Q
中科院分区：
文献类型：
--
作者：
Li S;Armstrong N;Zhao H;Hou W;Liu J;Chen C;Wan J;Wang W;Zhong C;Liu C;Zhu H;Xia N;Cheng T;Tang Q
寨卡病毒（ZIKV）被定义为导致法属波利尼西亚、巴西、波多黎各和其他南美国家小头畸形病例数量增加的致畸病原体。使用动物模型的实验研究在了解病毒发病机制、传播、致畸机制和病毒与宿主相互作用方面取得了巨大的进展。然而，已发表的研究中使用的动物大多是干扰素 (IFN) 受损的，无论是遗传原因还是抗体治疗。在此，我们使用非洲株（MR766）和亚洲株（PRVABC59 和 SZ-WIV01）研究了 IFN 活性小鼠中的 ZIKV 感染。通过对四种不同品种的小鼠进行测试，我们发现BALB/c新生小鼠对ZIKV感染具有抵抗力，昆明、ICR和C57BL/6新生小鼠对ZIKV感染具有致命性易感性，并且C57BL/6新生小鼠1至3天龄的死亡呈病毒剂量依赖性。大脑的大小和重量显着减小，感染ZIKV的小鼠出现后肢麻痹、震颤、行走平衡能力差等神经元症状。病理和免疫荧光实验表明，寨卡病毒感染中枢神经系统（CNS）的不同区域，包括灰质、海马、大脑皮层和脊髓，但不感染嗅球。有趣的是，ZIKV 在多个器官中复制并导致肝脏和睾丸发病，这意味着 ZIKV 感染可能通过产后感染给新生儿带来很高的健康风险。总之，我们使用非 IFN 受损的动物模型研究了 ZIKV 发病机制。
Zika virus (ZIKV) has been defined as a teratogenic pathogen behind the increased number of cases of microcephaly in French Polynesia, Brazil, Puerto Rico, and other South American countries. Experimental studies using animal models have achieved tremendous insight into understanding the viral pathogenesis, transmission, teratogenic mechanisms, and virus–host interactions. However, the animals used in published investigations are mostly interferon (IFN)-compromised, either genetically or via antibody treatment. Herein, we studied ZIKV infection in IFN-competent mice using African (MR766) and Asian strains (PRVABC59 and SZ-WIV01). After testing four different species of mice, we found that BALB/c neonatal mice were resistant to ZIKV infection, that Kunming, ICR and C57BL/6 neonatal mice were fatally susceptible to ZIKV infection, and that the fatality of C57BL/6 neonates from 1 to 3 days old were in a viral dose-dependent manner. The size and weight of the brain were significantly reduced, and the ZIKV-infected mice showed neuronal symptoms such as hind-limb paralysis, tremor, and poor balance during walking. Pathologic and immunofluorescent experiments revealed that ZIKV infected different areas of the central nervous system (CNS) including gray matter, hippocampus, cerebral cortex, and spinal cord, but not olfactory bulb. Interestingly, ZIKV replicated in multiple organs and resulted in pathogenesis in liver and testis, implying that ZIKV infection may engender a high health risk in neonates by postnatal infection. In summary, we investigated ZIKV pathogenesis using an animal model that is not IFN-compromised.