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Differential Responses of Human Fetal Brain Neural Stem Cells to Zika Virus Infection
Erica L. McGrath10
, Shannan L. Rossi10
, Junling Gao10
, 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 Fern?ndez-Salas
, Scott C. Weaver
, Nikos Vasilakis
Correspondence information about the author Nikos Vasilakis
Email the author Nikos Vasilakis
, Ping WuCorrespondence information about the author Ping WuEmail the author Ping Wu
10Co-first author
Published Online: February 16, 2017
Publication stage: In Press Corrected Proof
Highlights
Summary
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.
full article
Erica L. McGrath10
, Shannan L. Rossi10
, Junling Gao10
, 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 Fern?ndez-Salas
, Scott C. Weaver
, Nikos Vasilakis
Correspondence information about the author Nikos VasilakisEmail the author Nikos Vasilakis, Ping Wu
Correspondence information about the author Ping WuEmail the author Ping Wu10Co-first author
Published Online: February 16, 2017
Publication stage: In Press Corrected Proof
Highlights
- ? Mexican ZIKV strain infects primary human fetal brain-derived neural stem cells
- ? ZIKV inhibits neuronal differentiation in a cell-strain-dependent manner
- ? Majority of differentiated ZIKV-infected cells are glial cells
- ? ZIKV-mediated transcriptome alteration is cell-strain-dependent
Summary
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.
full article
