Zika virus (ZIKV) is a mosquito-borne Flavivirus that causes Zika disease with particular neurological complications, including Guillain-Barré Syndrome and congenital microcephaly. Although ZIKV has been shown to directly infect human neural progenitor cells (hNPCs), thereby decreasing their viability and growth, it is as yet unknown which of the cellular pathways involved in the disruption of neurogenesis are affected following ZIKV infection. By comparing the effect of two ZIKV strains in vitro on hNPCs, the differentiation process of the latter cells was found to lead to a decreased susceptibility to infection and cell death induced by each of the ZIKV strains, which was associated with an earlier and stronger antiviral innate immune response in infected, differentiated hNPCs, as compared to undifferentiated cells. Moreover, ZIKV modulated, both in hNPCs and in vivo in fetal brain in an experimental mouse model, the expression of the Notch pathway which is involved in cellular proliferation, apoptosis and differentiation during neurogenesis. These results show that the differentiation state of hNPCs is a significant factor contributing to the outcome of ZIKV infection and furthermore suggest that ZIKV infection might initiate early activation of the Notch pathway resulting in an abnormal differentiation process, implicated in ZIKV-induced brain injury.

中文翻译：

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寨卡病毒根据人类神经祖细胞的分化状态进行差异性感染，并通过 Notch 途径失调神经发生。

寨卡病毒 (ZIKV) 是一种蚊媒黄病毒，会导致寨卡病并伴有特定的神经系统并发症，包括格林-巴利综合征和先天性小头畸形。尽管 ZIKV 已被证明可以直接感染人类神经祖细胞 (hNPC)，从而降低其活力和生长，但目前尚不清楚哪些参与神经发生破坏的细胞途径在 ZIKV 感染后受到影响。通过比较两种ZIKV毒株在体外对hNPCs的影响，发现后一种细胞的分化过程导致对每种ZIKV毒株诱导的感染和细胞死亡的易感性降低，这与更早更强的抗病毒作用有关。与未分化细胞相比，受感染的分化 hNPC 中的先天免疫反应。此外，ZIKV 在 hNPC 和实验小鼠模型中的胎脑体内调节 Notch 通路的表达，该通路参与神经发生过程中的细胞增殖、凋亡和分化。这些结果表明，hNPCs 的分化状态是导致 ZIKV 感染结果的重要因素，并且进一步表明，ZIKV 感染可能启动 Notch 通路的早期激活，导致异常分化过程，与 ZIKV 诱导的脑损伤有关。