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

Erica L. McGrath, Shannan Rossi, Junling Gao, Steven Widen, Auston C. Grant, Tiffany J. Dunn, Sasha R. Azar, Christopher M. Roundy, Ying Xiong, Deborah J. Prusak, Bradford Loucas, Thomas Wood, Yongjia Yu, Ildefonso Fernández-Salas, Scott Weaver, Nikos Vasilakis, Ping Wu

Research output: Contribution to journalArticle

42 Citations (Scopus)

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. In this article, Wu, Vasilakis, and colleagues demonstrate the infection of primary human fetal brain-derived neural stem cells by a 2015 Mexican strain of ZIKV. They show that ZIKV is cytotoxic and inhibits proliferation independent of different human origins, but inhibits neuronal differentiation and alters gene expression in a cell-strain-dependent manner.

Original languageEnglish (US)
JournalStem Cell Reports
DOIs
StateAccepted/In press - Jul 27 2016

Fingerprint

Neural Stem Cells
Stem cells
Viruses
Brain Stem
Brain
Microcephaly
Infection
Zika Virus Infection
Transcriptome
Individuality
Disease Outbreaks
Zika Virus
Gene expression
Stem Cells
Mothers
Gene Expression

Keywords

  • Astrocyte
  • Differentiation
  • Human neural stem cell
  • Innate immunity
  • Neurogenesis
  • Neuron
  • Proliferation
  • Transcriptome
  • Zika virus

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

Cite this

Differential Responses of Human Fetal Brain Neural Stem Cells to Zika Virus Infection. / McGrath, Erica L.; Rossi, Shannan; Gao, Junling; Widen, Steven; Grant, Auston C.; Dunn, Tiffany J.; Azar, Sasha R.; Roundy, Christopher M.; Xiong, Ying; Prusak, Deborah J.; Loucas, Bradford; Wood, Thomas; Yu, Yongjia; Fernández-Salas, Ildefonso; Weaver, Scott; Vasilakis, Nikos; Wu, Ping.

In: Stem Cell Reports, 27.07.2016.

Research output: Contribution to journalArticle

McGrath, Erica L. ; Rossi, Shannan ; Gao, Junling ; Widen, Steven ; Grant, Auston C. ; Dunn, Tiffany J. ; Azar, Sasha R. ; Roundy, Christopher M. ; Xiong, Ying ; Prusak, Deborah J. ; Loucas, Bradford ; Wood, Thomas ; Yu, Yongjia ; Fernández-Salas, Ildefonso ; Weaver, Scott ; Vasilakis, Nikos ; Wu, Ping. / Differential Responses of Human Fetal Brain Neural Stem Cells to Zika Virus Infection. In: Stem Cell Reports. 2016.
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AU - Grant, Auston C.

AU - Dunn, Tiffany J.

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AU - Loucas, Bradford

AU - Wood, Thomas

AU - Yu, Yongjia

AU - Fernández-Salas, Ildefonso

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AU - Vasilakis, Nikos

AU - Wu, Ping

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AB - 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. In this article, Wu, Vasilakis, and colleagues demonstrate the infection of primary human fetal brain-derived neural stem cells by a 2015 Mexican strain of ZIKV. They show that ZIKV is cytotoxic and inhibits proliferation independent of different human origins, but inhibits neuronal differentiation and alters gene expression in a cell-strain-dependent manner.

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