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.
authors.affiliation: Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA. Electronic address: tang@bio.fsu.edu.
authors.forename: Hengli
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA.
authors.forename: Christy
authors.initials: C
authors.lastname: Hammack
authors.affiliation: Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Ogden
authors.affiliation: 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.
authors.forename: Zhexing
authors.initials: Z
authors.lastname: Wen
authors.affiliation: 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.
authors.forename: Xuyu
authors.initials: X
authors.lastname: Qian
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Yujing
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: Yao
authors.affiliation: 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.
authors.forename: Jaehoon
authors.initials: J
authors.lastname: Shin
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Feiran
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA.
authors.forename: Emily M
authors.initials: EM
authors.lastname: Lee
authors.affiliation: 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.
authors.forename: Kimberly M
authors.initials: KM
authors.lastname: Christian
authors.affiliation: College of Medicine, Florida State University, Tallahassee, FL 32306, USA.
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Didier
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Jin
authors.affiliation: 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.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Song
authors.affiliation: 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.
authors.forename: Guo-Li
authors.initials: GL
authors.lastname: Ming
mesh_terms: D002453:Cell Cycle; D016923:Cell Death; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000821:virology; D058953:Neural Stem Cells / Q000473:pathology* / Q000821:virology*; D000071244:Zika Virus / Q000502:physiology*; D000071243:Zika Virus Infection / Q000473:pathology* / Q000821:virology*