Differential Responses of Human Fetal Brain Neural Stem Cells to Zika Virus Infection

Stem Cell Reports. 2017 Mar 14;8(3):715-727. doi: 10.1016/j.stemcr.2017.01.008. Epub 2017 Feb 16.

Abstract

Zika virus (ZIKV) infection causes microcephaly in a subset of infants born to infected pregnant mothers. It is unknown whether human individual differences contribute to differential susceptibility of ZIKV-related neuropathology. Here, we use an Asian-lineage ZIKV strain, isolated from the 2015 Mexican outbreak (Mex1-7), to infect primary human neural stem cells (hNSCs) originally derived from three individual fetal brains. All three strains of hNSCs exhibited similar rates of Mex1-7 infection and reduced proliferation. However, Mex1-7 decreased neuronal differentiation in only two of the three stem cell strains. Correspondingly, ZIKA-mediated transcriptome alterations were similar in these two strains but significantly different from that of the third strain with no ZIKV-induced neuronal reduction. This study thus confirms that an Asian-lineage ZIKV strain infects primary hNSCs and demonstrates a cell-strain-dependent response of hNSCs to ZIKV infection.

Keywords: Zika virus; astrocyte; differentiation; human neural stem cell; innate immunity; neurogenesis; neuron; proliferation; transcriptome.

MeSH terms

  • Animals
  • Astrocytes
  • Brain / immunology
  • Brain / metabolism*
  • Brain / virology*
  • Cell Differentiation
  • Cell Proliferation
  • Cell Survival
  • Chlorocebus aethiops
  • Cluster Analysis
  • Fetus
  • Gene Expression
  • Gene Expression Profiling
  • Humans
  • Immunity, Innate
  • Male
  • Mice
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism*
  • Neural Stem Cells / virology*
  • Neurogenesis / genetics
  • Neurons
  • Transcriptome
  • Vero Cells
  • Zika Virus / classification
  • Zika Virus / physiology*
  • Zika Virus Infection / genetics
  • Zika Virus Infection / immunology
  • Zika Virus Infection / metabolism
  • Zika Virus Infection / virology*