Zika Virus Infects Human Cortical Neural Progenitors and Attenuates Their Growth
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 mosqui...
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| Published in | Cell stem cell Vol. 18; no. 5; pp. 587 - 590 |
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| Main Authors | , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Elsevier Inc
05.05.2016
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| Subjects | |
| Online Access | Get full text |
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| 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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•Zika virus (ZIKV) infects human embryonic cortical neural progenitor cells (hNPCs)•ZIKV-infected hNPCs produce infectious ZIKV particles•ZIKV infection leads to increased cell death of hNPCs•ZIKV infection dysregulates cell cycle and transcription in hNPCs
The suspected link between ZIKV infection and microcephaly is an urgent global health concern. Tang et al. report that ZIKV virus directly infects human cortical neural progenitor cells with high efficiency, resulting in stunted growth of this cell population and transcriptional dysregulation. |
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| AbstractList | 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. 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. [Display omitted] •Zika virus (ZIKV) infects human embryonic cortical neural progenitor cells (hNPCs)•ZIKV-infected hNPCs produce infectious ZIKV particles•ZIKV infection leads to increased cell death of hNPCs•ZIKV infection dysregulates cell cycle and transcription in hNPCs The suspected link between ZIKV infection and microcephaly is an urgent global health concern. Tang et al. report that ZIKV virus directly infects human cortical neural progenitor cells with high efficiency, resulting in stunted growth of this cell population and transcriptional dysregulation. |
| Author | Lee, Emily M. Ming, Guo-li Tang, Hengli Wen, Zhexing Christian, Kimberly M. Yao, Bing Didier, Ruth A. Hammack, Christy Shin, Jaehoon Li, Yujing Zhang, Feiran Qian, Xuyu Ogden, Sarah C. Jin, Peng Song, Hongjun |
| Author_xml | – sequence: 1 givenname: Hengli surname: Tang fullname: Tang, Hengli email: tang@bio.fsu.edu organization: Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA – sequence: 2 givenname: Christy surname: Hammack fullname: Hammack, Christy organization: Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA – sequence: 3 givenname: Sarah C. surname: Ogden fullname: Ogden, Sarah C. organization: Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA – sequence: 4 givenname: Zhexing surname: Wen fullname: Wen, Zhexing organization: Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21025, USA – sequence: 5 givenname: Xuyu surname: Qian fullname: Qian, Xuyu organization: Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21025, USA – sequence: 6 givenname: Yujing surname: Li fullname: Li, Yujing organization: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA – sequence: 7 givenname: Bing surname: Yao fullname: Yao, Bing organization: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA – sequence: 8 givenname: Jaehoon surname: Shin fullname: Shin, Jaehoon organization: Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21025, USA – sequence: 9 givenname: Feiran surname: Zhang fullname: Zhang, Feiran organization: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA – sequence: 10 givenname: Emily M. surname: Lee fullname: Lee, Emily M. organization: Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA – sequence: 11 givenname: Kimberly M. surname: Christian fullname: Christian, Kimberly M. organization: Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21025, USA – sequence: 12 givenname: Ruth A. surname: Didier fullname: Didier, Ruth A. organization: College of Medicine, Florida State University, Tallahassee, FL 32306, USA – sequence: 13 givenname: Peng surname: Jin fullname: Jin, Peng organization: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA – sequence: 14 givenname: Hongjun surname: Song fullname: Song, Hongjun email: shongju1@jhmi.edu organization: Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21025, USA – sequence: 15 givenname: Guo-li surname: Ming fullname: Ming, Guo-li email: gming1@jhmi.edu organization: Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21025, USA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/26952870$$D View this record in MEDLINE/PubMed |
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| SubjectTerms | Cell Cycle Cell Death Cell Proliferation Flavivirus Gene Expression Regulation Humans Induced Pluripotent Stem Cells - virology Neural Stem Cells - pathology Neural Stem Cells - virology Zika virus Zika Virus - physiology Zika Virus Infection - pathology Zika Virus Infection - virology |
| Title | Zika Virus Infects Human Cortical Neural Progenitors and Attenuates Their Growth |
| URI | https://dx.doi.org/10.1016/j.stem.2016.02.016 https://www.ncbi.nlm.nih.gov/pubmed/26952870 https://www.proquest.com/docview/1787472220 https://www.proquest.com/docview/1808705598 |
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