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H Tang, C Hammack, SC Ogden, Z Wen, X Qian, Y Li, B Yao, J Shin, F Zhang, EM Lee, KM Christian, RA Didier, P Jin, H Song and GL Ming
Abstract
The suspected link between infection by Zika virus (ZIKV), a re-emerging flavivirus, and microcephaly is an urgent global health concern. The direct target cells of ZIKV in the developing human fetus are not clear. Here we show that a strain of the ZIKV, MR766, serially passaged in monkey and mosquito cells efficiently infects human neural progenitor cells (hNPCs) derived from induced pluripotent stem cells. Infected hNPCs further release infectious ZIKV particles. Importantly, ZIKV infection increases cell death and dysregulates cell-cycle progression, resulting in attenuated hNPC growth. Global gene expression analysis of infected hNPCs reveals transcriptional dysregulation, notably of cell-cycle-related pathways. Our results identify hNPCs as a direct ZIKV target. In addition, we establish a tractable experimental model system to investigate the impact and mechanism of ZIKV on human brain development and provide a platform to screen therapeutic compounds.
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Concepts
Infection, Stem cell, Nervous system, DNA, Progenitor cell, Gene expression, Gene, Developmental biology
MeSH headings
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