Genetic Ablation of AXL Does Not Protect Human Neural Progenitor Cells and Cerebral Organoids from Zika Virus Infection
Genetic Ablation of AXL Does Not Protect Human Neural Progenitor Cells and Cerebral Organoids from Zika Virus Infection
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DOI：
10.1016/j.stem.2016.11.011
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发表时间：
2016-12-01
期刊：
影响因子：
23.9
通讯作者：
Eggan, Kevin
中科院分区：
文献类型：
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作者：
Wells, Michael F.;Salick, Max R.;Eggan, Kevin
寨卡病毒（ZIKV）可以穿过胎盘屏障，导致胎儿大脑感染和包括小头畸形在内的神经缺陷。目前正在深入研究寨卡病毒的细胞趋向性和病毒利用附着因子进入参与发病的关键细胞类型的特性。初步研究表明ZIKV优先靶向神经祖细胞（NPCs），这为在某些妊娠中观察到的发育表型提供了解释。AXL蛋白已被提名为包括npc在内的几种细胞类型中ZIKV的关键附着因子。然而，本研究表明，在人诱导多能干细胞（iPSC）衍生的npc或脑类器官中，AXL的基因消融对ZIKV进入或ZIKV介导的细胞死亡没有影响。这些发现对AXL抑制剂在预防感染后出生缺陷方面的效用提出了质疑，并表明需要进一步研究npc中的病毒附着因子。
Zika virus (ZIKV) can cross the placental barrier, resulting in infection of the fetal brain and neurological defects including microcephaly. The cellular tropism of ZIKV and the identity of attachment factors used by the virus to gain access to key cell types involved in pathogenesis are under intense investigation. Initial studies suggested that ZIKV preferentially targets neural progenitor cells (NPCs), providing an explanation for the developmental phenotypes observed in some pregnancies. The AXL protein has been nominated as a key attachment factor for ZIKV in several cell types including NPCs. However, here we show that genetic ablation of AXL has no effect on ZIKV entry or ZIKV-mediated cell death in human induced pluripotent stem cell (iPSC)-derived NPCs or cerebral organoids. These findings call into question the utility of AXL inhibitors for preventing birth defects after infection and suggest that further studies of viral attachment factors in NPCs are needed.