Zika virus-induces metabolic alterations in fetal neuronal progenitors that could influence in neurodevelopment during early pregnancy
Zika virus-induces metabolic alterations in fetal neuronal progenitors that could influence in neurodevelopment during early pregnancy
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DOI：
10.1101/2022.08.24.505080
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发表时间：
2022-08
期刊：
影响因子：
2.4
通讯作者：
Javier Gilbert-Jaramillo;Ujang Purnama;Z. Molnár;W. James
中科院分区：
文献类型：
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作者：
Javier Gilbert-Jaramillo;Ujang Purnama;Z. Molnár;W. James
神经前体亚型有不同的命运限制，受依赖时间的能量通路激活的调节。因此，寨卡病毒(ZIKV)劫持细胞代谢以支持其复制可能会对发育中的胎儿大脑造成损害。在这里，我们发现ZIKV在两个糖酵解不同的HiPSC衍生的神经元前体细胞中复制不同，这两个神经前体细胞对应于前脑的早期和晚期前体细胞。这种差异复制改变了代谢基因的转录，并上调了前体亚型的糖酵解能力。Imagestream®分析显示，在感染的早期阶段，ZIKV在早期祖细胞中的复制增加了脂滴的丰度，降低了线粒体的大小和膜电位。在感染的后期，早期祖细胞表现出更多的脂滴在亚细胞内的分布，而晚期祖细胞表现出线粒体尺寸的减小。在ZIKV感染期间存在高鼻咽癌亚型特异性细胞代谢改变的发现可能有助于解释不同孕期脑损伤的差异。
Neuronal progenitor subtypes have distinct fate restrictions regulated by time-dependent activation of energetic pathways. Thus, the hijacking of cellular metabolism by Zika virus (ZIKV) to support its replication may contribute to damage in the developing fetal brain. Here, we showed that ZIKV replicates differently in two glycolytically distinct hiPSC-derived neuronal progenitors that correspond to early and late progenitors in the forebrain. This differential replication alters the transcription of metabolic genes and upregulates the glycolytic capacity of progenitor subtypes. Analysis using Imagestream® revealed that, during early stages of infection, ZIKV replication in early progenitors increases lipid droplet abundance and decreases mitochondrial size and membrane potential. During later stages infection, early progenitors show increased subcellular distribution of lipid droplets, whilst late progenitors show decreased mitochondria size. The finding that there are hi-NPC subtype-specific alterations of cellular metabolism during ZIKV infection may help to explain the differences in brain damage over each trimester.