Zika virus infection leads to mitochondrial failure, oxidative stress and DNA damage in human iPSC-derived astrocytes
Zika virus infection leads to mitochondrial failure, oxidative stress and DNA damage in human iPSC-derived astrocytes
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DOI：
10.1038/s41598-020-57914-x
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发表时间：
2020-01-27
影响因子：
4.6
通讯作者：
Rehen, Stevens Kastrup
中科院分区：
文献类型：
--
作者：
Ledur, Pitia Flores;Karmirian, Karina;Rehen, Stevens Kastrup
寨卡病毒（ZIKV）由于与先天性畸形有关而被广泛研究，最近的研究表明星形胶质细胞是ZIKV的靶点。然而，ZIKV感染的后果，特别是对这种细胞类型的后果，在很大程度上仍然是未知的，特别是考虑到旨在了解病毒神经毒性中涉及的关键细胞机制和命运之间的串扰的综合研究。在此，呈现了ZIKV感染在iPSC衍生的星形胶质细胞中的结果。我们的研究结果显示，ROS失衡，线粒体缺陷和DNA断裂，这些都与神经系统疾病有关。我们还检测到神经胶质反应，也存在于小鼠和巴西东北部感染新生儿的死后大脑中。鉴于神经胶质细胞在大脑发育中的作用，这些发现可能有助于解释先天性寨卡综合征中观察到的与神经元丢失和运动缺陷有关的影响。
Zika virus (ZIKV) has been extensively studied since it was linked to congenital malformations, and recent research has revealed that astrocytes are targets of ZIKV. However, the consequences of ZIKV infection, especially to this cell type, remain largely unknown, particularly considering integrative studies aiming to understand the crosstalk among key cellular mechanisms and fates involved in the neurotoxicity of the virus. Here, the consequences of ZIKV infection in iPSC-derived astrocytes are presented. Our results show ROS imbalance, mitochondrial defects and DNA breakage, which have been previously linked to neurological disorders. We have also detected glial reactivity, also present in mice and in post-mortem brains from infected neonates from the Northeast of Brazil. Given the role of glia in the developing brain, these findings may help to explain the observed effects in congenital Zika syndrome related to neuronal loss and motor deficit.