Zika virus (ZIKV) can generate a number of neurological dysfunctions in infected humans. Here, we tested the potential of human immune cells to protect against ZIKV infection in genetically humanized MISTRG mice. FACS analysis showed robust reconstitution of the mouse spleen with human T cells. Peripheral ZIKV inoculation resulted in infection within the brains of MISTRG mice. Mice that were reconstituted with human peripheral blood mononuclear cells (PBMC) showed a more rapid lethal response to ZIKV than the control mice lacking these immune cells. Immunocytochemical analysis of T cell markers CD3, CD45, or CD8 showed strong T cell presence in the brain, together with robust infection by ZIKV particularly in the excitatory pyramidal and granule neurons of the hippocampus. Infection was also found in cortex, striatum, the dopamine neurons of the substantia nigra, and other brain loci. Infection was considerably less in other regions such as the septum and hypothalamus. These data support the perspective that, rather than exerting a protective function, T cells may underlie some ZIKV-mediated neuropathology in the brain.

中文翻译：

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免疫细胞增强了具有人源化免疫系统的小鼠大脑中寨卡病毒介导的神经功能障碍

寨卡病毒 (ZIKV) 可在受感染的人类中产生许多神经功能障碍。在这里，我们测试了人类免疫细胞保护基因人源化 MISTRG 小鼠免受 ZIKV 感染的潜力。FACS 分析显示用人 T 细胞对小鼠脾脏进行了强有力的重建。外周 ZIKV 接种导致 MISTRG 小鼠脑内感染。与缺乏这些免疫细胞的对照小鼠相比，用人外周血单个核细胞 (PBMC) 重组的小鼠对 ZIKV 的致死反应更快。T 细胞标志物 CD3、CD45 或 CD8 的免疫细胞化学分析显示大脑中存在强 T 细胞，以及 ZIKV 的强烈感染，特别是在海马的兴奋性锥体和颗粒神经元中。皮层、纹状体、黑质和其他大脑部位的多巴胺神经元。其他区域如隔膜和下丘脑的感染要少得多。这些数据支持这样的观点，即 T 细胞可能是大脑中某些 ZIKV 介导的神经病理学的基础，而不是发挥保护功能。