Differential Responses of Human Fetal Brain Neural Stem Cells to Zika Virus Infection

人类胎儿脑神经干细胞对寨卡病毒感染的不同反应

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作者:Erica L McGrath, Shannan L Rossi, Junling Gao, Steven G Widen, Auston C Grant, Tiffany J Dunn, Sasha R Azar, Christopher M Roundy, Ying Xiong, Deborah J Prusak, Bradford D Loucas, Thomas G Wood, Yongjia Yu, Ildefonso Fernández-Salas, Scott C Weaver, Nikos Vasilakis, Ping Wu

Abstract

Zika virus (ZIKV) infection causes microcephaly in a subset of infants born to infected pregnant mothers. It is unknown whether human individual differences contribute to differential susceptibility of ZIKV-related neuropathology. Here, we use an Asian-lineage ZIKV strain, isolated from the 2015 Mexican outbreak (Mex1-7), to infect primary human neural stem cells (hNSCs) originally derived from three individual fetal brains. All three strains of hNSCs exhibited similar rates of Mex1-7 infection and reduced proliferation. However, Mex1-7 decreased neuronal differentiation in only two of the three stem cell strains. Correspondingly, ZIKA-mediated transcriptome alterations were similar in these two strains but significantly different from that of the third strain with no ZIKV-induced neuronal reduction. This study thus confirms that an Asian-lineage ZIKV strain infects primary hNSCs and demonstrates a cell-strain-dependent response of hNSCs to ZIKV infection.

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