Zika virus (ZIKV) infection is a serious public threat with cases reported in about 70 countries and territories. One of the most serious consequences of ZIKV infection is congenital microcephaly in babies. Congenital microcephaly has been suggested to result from infection of neural progenitor cells (NPCs) in the developing fetal brain. However, the molecular and cellular mechanisms underlying microcephaly development remains to be fully elucidated. In this study, we employed quantitative proteomics to determine protein expression profile that occur during viral replication in NPCs. Bioinformatics analysis of the protein expression changes resulted in the identification of a wide range of cell signaling pathways. Specifically, pathways involved in neurogenesis and embryonic development were markedly altered, along with those associated with cell cycle, apoptosis, lipid metabolism and oxidative stress. Notably, the differential regulation of Ephrin Receptor and PPAR signaling pathways, as revealed by quantitative proteomics and validated by qPCR array, underscores the need to explore these pathways in disease development. Collectively, these results indicate that ZIKV-induced pathogenesis involves complex virus-host reactions; the findings reported here could help shed light on the mechanisms underlying ZIKV-induced microcephaly and ZIKV replication in NPCs.

寨卡病毒（ZIKV）感染是一种严重的公共威胁，在大约70个国家和地区报告了病例。ZIKV感染最严重的后果之一是婴儿的先天性小头畸形。已建议先天性小头畸形是由发育中的胎儿脑中神经祖细胞（NPC）感染引起的。然而，小头畸形发展的分子和细胞机制仍有待充分阐明。在这项研究中，我们采用定量蛋白质组学来确定在NPC中病毒复制过程中发生的蛋白质表达谱。蛋白质表达变化的生物信息学分析导致​​鉴定了广泛的细胞信号通路。具体来说，涉及神经发生和胚胎发育的途径被显着改变，以及与细胞周期，细胞凋亡，脂质代谢和氧化应激相关的那些。值得注意的是，通过定量蛋白质组学揭示并通过qPCR阵列验证的Ephrin受体和PPAR信号通路的差异调节强调了在疾病发展中探索这些通路的必要性。总体而言，这些结果表明ZIKV诱导的发病机制涉及复杂的病毒宿主反应。此处报道的发现可能有助于阐明ZIKV诱导的NPC小头畸形和ZIKV复制的机制。这些结果表明ZIKV诱导的发病机制涉及复杂的病毒宿主反应。此处报道的发现可能有助于阐明ZIKV诱导的NPC小头畸形和ZIKV复制的机制。这些结果表明ZIKV诱导的发病机制涉及复杂的病毒宿主反应。此处报道的发现可能有助于阐明ZIKV诱导的NPC小头畸形和ZIKV复制的机制。