Zika Virus Alters DNA Methylation of Neural Genes in an Organoid Model of the Developing Human Brain
Zika Virus Alters DNA Methylation of Neural Genes in an Organoid Model of the Developing Human Brain
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DOI：
10.1128/msystems.00210-17
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发表时间：
2018-01-01
期刊：
影响因子：
6.4
通讯作者：
Zwaka, Thomas P.
中科院分区：
文献类型：
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作者：
Janssens, Syvie;Schotsaert, Michael;Zwaka, Thomas P.
妊娠早期感染寨卡病毒（ZIKV）可导致出生时的小头畸形和相关缺陷，但它是否会诱发日后出现的神经系统后遗症仍不清楚。使用基于胚胎干细胞衍生的脑类器官的发育中的脑模型，我们研究了ZIKV感染对选定神经细胞类型中整个基因组的DNA甲基化模式的影响。该病毒出乎意料地改变了神经祖细胞、星形胶质细胞和分化的神经元的DNA甲基化组，这些基因与许多脑疾病的发病机制有关，最突出的是精神发育迟滞和精神分裂症。我们的研究结果表明，胎儿发育期间的ZIKV感染可能导致一系列迟发性神经精神并发症。关于人类神经干细胞和脑类器官的科学研究已经证实了寨卡病毒的先天性嗜神经性和神经破坏性。然而，产前ZIKV感染与更微妙的大脑改变（如表观遗传变化）相关的程度仍然不清楚。在这里，我们解决了ZIKV感染是否会诱导DNA甲基化变化，从而可能在以后的生活中导致大脑疾病的问题。
Zika virus (ZIKV) infection during early pregnancy can cause microcephaly and associated defects at birth, but whether it can induce neurologic sequelae that appear later in life remains unclear. Using a model of the developing brain based on embryonic stem cell-derived brain organoids, we studied the impact of ZIKV infection on the DNA methylation pattern across the entire genome in selected neural cell types. The virus unexpectedly alters the DNA methylome of neural progenitors, astrocytes, and differentiated neurons at genes that have been implicated in the pathogenesis of a number of brain disorders, most prominently mental retardation and schizophrenia. Our results suggest that ZIKV infection during fetal development could lead to a spectrum of delayed-onset neuropsychiatric complications. IMPORTANCE Scientific research on human neural stem cells and cerebral organoids has confirmed the congenital neurotropic and neurodestructive nature of the Zika virus. However, the extent to which prenatal ZIKV infection is associated with more subtle brain alterations, such as epigenetic changes, remains ill defined. Here, we address the question of whether ZIKV infection induces DNA methylation changes with the potential to cause brain disorders later in life.