Zika virus infects human cortical neural progenitors and attenuates their growth

Hengli Tang; Christy Hammack; Sarah C. Ogden; Zhexing Wen; Xuyu Qian; Yujing Li; Bing Yao; Jaehoon Shin; Feiran Zhang; Emily M. Lee; Kimberly M. Christian; Ruth A. Didier; Peng Jin; Hongjun Song; Guo Li Ming

doi:10.1016/j.stem.2016.02.016

Zika virus infects human cortical neural progenitors and attenuates their growth

Hengli Tang, Christy Hammack, Sarah C. Ogden, Zhexing Wen, Xuyu Qian, Yujing Li, Bing Yao, Jaehoon Shin, Feiran Zhang, Emily M. Lee, Kimberly M. Christian, Ruth A. Didier, Peng Jin, Hongjun Song, Guo Li Ming

School of Medicine

Research output: Contribution to journal › Article › peer-review

769 Scopus citations

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.

Original language	English (US)
Pages (from-to)	587-590
Number of pages	4
Journal	Cell stem cell
Volume	18
Issue number	5
DOIs	https://doi.org/10.1016/j.stem.2016.02.016
State	Published - May 5 2016

ASJC Scopus subject areas

Molecular Medicine
Genetics
Cell Biology

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10.1016/j.stem.2016.02.016

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@article{421da5d517a64ca89a6a9c8f4fe381e1,

title = "Zika virus infects human cortical neural progenitors and attenuates their growth",

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.",

author = "Hengli Tang and Christy Hammack and Ogden, {Sarah C.} and Zhexing Wen and Xuyu Qian and Yujing Li and Bing Yao and Jaehoon Shin and Feiran Zhang and Lee, {Emily M.} and Christian, {Kimberly M.} and Didier, {Ruth A.} and Peng Jin and Hongjun Song and Ming, {Guo Li}",

note = "Funding Information: We thank Yichen Cheng, Taylor Lee, and Jianshe Lang of the Tang laboratory, Lihong Liu and Yuan Cai of the Ming and Song laboratories, Luoxiu Huang of the Jin laboratory for technical assistance, Zhiheng Xu and additional laboratory members for suggestions, and Timothy Megraw for assistance with confocal imaging. H.T. thanks the College of Arts and Sciences and the Department of Biological Science at Florida State University for seed 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 funding (to H.S.). Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",

year = "2016",

month = may,

day = "5",

doi = "10.1016/j.stem.2016.02.016",

language = "English (US)",

volume = "18",

pages = "587--590",

journal = "Cell stem cell",

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T1 - Zika virus infects human cortical neural progenitors and attenuates their growth

AU - Tang, Hengli

AU - Hammack, Christy

AU - Ogden, Sarah C.

AU - Wen, Zhexing

AU - Qian, Xuyu

AU - Li, Yujing

AU - Yao, Bing

AU - Shin, Jaehoon

AU - Zhang, Feiran

AU - Lee, Emily M.

AU - Christian, Kimberly M.

AU - Didier, Ruth A.

AU - Jin, Peng

AU - Song, Hongjun

AU - Ming, Guo Li

N1 - Funding Information: We thank Yichen Cheng, Taylor Lee, and Jianshe Lang of the Tang laboratory, Lihong Liu and Yuan Cai of the Ming and Song laboratories, Luoxiu Huang of the Jin laboratory for technical assistance, Zhiheng Xu and additional laboratory members for suggestions, and Timothy Megraw for assistance with confocal imaging. H.T. thanks the College of Arts and Sciences and the Department of Biological Science at Florida State University for seed 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 funding (to H.S.). Publisher Copyright: © 2016 Elsevier Inc.

PY - 2016/5/5

Y1 - 2016/5/5

N2 - 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.

AB - 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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JF - Cell stem cell

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ER -

Zika virus infects human cortical neural progenitors and attenuates their growth

Abstract

ASJC Scopus subject areas

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