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

doi:10.1016/j.stemcr.2017.01.008

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

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92 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 language	English (US)
Pages (from-to)	715-727
Number of pages	13
Journal	Stem Cell Reports
Volume	8
Issue number	3
DOIs	https://doi.org/10.1016/j.stemcr.2017.01.008
State	Published - 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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10.1016/j.stemcr.2017.01.008

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McGrath, E. L., Rossi, S. L., Gao, J., Widen, S. G., Grant, A. C., Dunn, T. J., Azar, S. R., Roundy, C. M., Xiong, Y., Prusak, D. J., Loucas, B. D., Wood, T. G., Yu, Y., Fernández-Salas, I., Weaver, S. C., Vasilakis, N., & Wu, P. (2017). Differential Responses of Human Fetal Brain Neural Stem Cells to Zika Virus Infection. Stem Cell Reports, 8(3), 715-727. https://doi.org/10.1016/j.stemcr.2017.01.008

McGrath, EL, Rossi, SL, Gao, J, Widen, SG, Grant, AC, Dunn, TJ, Azar, SR, Roundy, CM, Xiong, Y, Prusak, DJ, Loucas, BD, Wood, TG, Yu, Y, Fernández-Salas, I, Weaver, SC , Vasilakis, N & Wu, P 2017, 'Differential Responses of Human Fetal Brain Neural Stem Cells to Zika Virus Infection', Stem Cell Reports, vol. 8, no. 3, pp. 715-727. https://doi.org/10.1016/j.stemcr.2017.01.008

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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.",

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AU - Grant, Auston C.

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AU - Azar, Sasha R.

AU - Roundy, Christopher M.

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AU - Prusak, Deborah J.

AU - Loucas, Bradford D.

AU - Wood, Thomas G.

AU - Yu, Yongjia

AU - Fernández-Salas, Ildefonso

AU - Weaver, Scott C.

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.

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

Abstract

Keywords

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