Zika virus replicates in adult human brain tissue and impairs synapses and memory in mice
Zika virus replicates in adult human brain tissue and impairs synapses and memory in mice
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DOI：
10.1038/s41467-019-11866-7
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发表时间：
2019-09-05
影响因子：
16.6
通讯作者：
Ferreira, Sergio T.
中科院分区：
文献类型：
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作者：
Figueiredo, Claudia P.;Barros-Aragao, Fernanda G. Q.;Ferreira, Sergio T.
据报道，感染寨卡病毒（ZIKV）的成年患者出现影响中枢神经系统的神经系统并发症，但其潜在机制尚不清楚。在这里，我们报告了ZIKV在人和小鼠成年脑组织中复制，以成熟神经元为目标。寨卡病毒优先靶向与记忆相关的大脑区域，抑制海马长期增强并诱导成年小鼠的记忆损伤。寨卡病毒感染可诱导tnf - α上调、小胶质细胞增生和补体系统蛋白C1q和C3上调。发现小胶质细胞在急性感染时吞噬海马突触前终末。中和tnf - α信号，阻断小胶质细胞激活或C1q/C3可预防寨卡病毒感染小鼠突触和记忆损伤。结果表明ZIKV通过异常激活tnf - α、小胶质细胞和补体诱导突触和记忆功能障碍。我们的发现建立了一种寨卡病毒影响成人大脑的机制，并指出需要评估认知缺陷作为寨卡病毒感染成人的潜在合并症。
Neurological complications affecting the central nervous system have been reported in adult patients infected by Zika virus (ZIKV) but the underlying mechanisms remain unknown. Here, we report that ZIKV replicates in human and mouse adult brain tissue, targeting mature neurons. ZIKV preferentially targets memory-related brain regions, inhibits hippocampal long-term potentiation and induces memory impairment in adult mice. TNF-alpha upregulation, microgliosis and upregulation of complement system proteins, C1q and C3, are induced by ZIKV infection. Microglia are found to engulf hippocampal presynaptic terminals during acute infection. Neutralization of TNF-alpha signaling, blockage of microglial activation or of C1q/C3 prevent synapse and memory impairment in ZIKV-infected mice. Results suggest that ZIKV induces synapse and memory dysfunction via aberrant activation of TNF-alpha, microglia and complement. Our findings establish a mechanism by which ZIKV affects the adult brain, and point to the need of evaluating cognitive deficits as a potential comorbidity in ZIKV-infected adults.