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

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

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)715-727
Number of pages13
JournalStem Cell Reports
Volume8
Issue number3
DOIs
StatePublished - Mar 14 2017

Keywords

  • Zika virus
  • astrocyte
  • differentiation
  • human neural stem cell
  • innate immunity
  • neurogenesis
  • neuron
  • proliferation
  • transcriptome

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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