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Author Notes:

Correspondence: tang@bio.fsu.edu (H.T.), shongju1@jhmi.edu (H.S.), gming1@jhmi.edu (G.-l.M.)

H.T, H.S. and G-l. Ming conceived of the research, designed the study, and wrote the manuscript. C.H., S.C.O., Z.W. and X.Q. performed experiments, analyzed data and contributed equally to this study. Y.L., B.Y., J.S., F.Z. P.J. performed RNA-seq analysis, E.M.L., K.M.C., R.A.D. contributed to additional data collection. All authors commented on the manuscript.

We thank Yichen Cheng, Taylor Lee, and Jianshe Lang of Tang lab, Lihong Liu and Yuan Cai of Ming and Song labs, Luoxiu Huang of Jin lab for technical assistance, Zhiheng Xu and additional lab members for suggestions, and Timothy Megraw for assistance with confocal imaging.

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Research Funding:

This work was partially supported by NIH (AI119530/AI111250 to H.T.; NS047344 to H.S., NS048271/NS095348 to G-l.M. and NS051630/NS079625/MH102690 to P.J.), MSCRF (to H.S.) and start-up fund (to H.S.).

H.T. thank the College of Arts and Sciences and Department of Biological Science at Florida State University for seed funding

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Cell & Tissue Engineering
  • Cell Biology
  • CELLS

Zika Virus Infects Human Cortical Neural Progenitors and Attenuates Their Growth

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Journal Title:

Cell Stem Cell

Volume:

Volume 18, Number 5

Publisher:

, Pages 587-590

Type of Work:

Article | Post-print: After Peer Review

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.

Copyright information:

© 2016 Elsevier Inc.

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