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

Cell Stem Cell. 2016 May 5;18(5):587-90. doi: 10.1016/j.stem.2016.02.016. Epub 2016 Mar 4.

Authors

Hengli Tang¹, Christy Hammack², Sarah C Ogden², Zhexing Wen³, Xuyu Qian⁴, Yujing Li⁵, Bing Yao⁵, Jaehoon Shin⁶, Feiran Zhang⁵, Emily M Lee², Kimberly M Christian³, Ruth A Didier⁷, Peng Jin⁵, Hongjun Song⁸, Guo-Li Ming⁹

Affiliations

¹ Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA. Electronic address: tang@bio.fsu.edu.
² Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA.
³ Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21025, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21025, USA.
⁴ Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21025, USA; Biomedical Engineering Graduate Program, Johns Hopkins University School of Medicine, Baltimore, MD 21025, USA.
⁵ Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
⁶ Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21025, USA; Cellular and Molecular Medicine Graduate Program, Johns Hopkins University School of Medicine, Baltimore, MD 21025, USA.
⁷ College of Medicine, Florida State University, Tallahassee, FL 32306, USA.
⁸ Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21025, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21025, USA; Cellular and Molecular Medicine Graduate Program, Johns Hopkins University School of Medicine, Baltimore, MD 21025, USA; Solomon Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21025, USA; Kavli Neuroscience Discovery Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21025, USA. Electronic address: shongju1@jhmi.edu.
⁹ Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21025, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21025, USA; Cellular and Molecular Medicine Graduate Program, Johns Hopkins University School of Medicine, Baltimore, MD 21025, USA; Solomon Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21025, USA; Kavli Neuroscience Discovery Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21025, USA; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21025, USA. Electronic address: gming1@jhmi.edu.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Cell Cycle
Cell Death
Cell Proliferation
Gene Expression Regulation
Humans
Induced Pluripotent Stem Cells / virology
Neural Stem Cells / pathology*
Neural Stem Cells / virology*
Zika Virus / physiology*
Zika Virus Infection / pathology*
Zika Virus Infection / virology*

Abstract

Publication types

MeSH terms

Grants and funding