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

Research output: Contribution to journal › Article › peer-review

96 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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title = "Differential Responses of Human Fetal Brain Neural Stem Cells to Zika Virus Infection",

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",

author = "McGrath, {Erica L.} and Rossi, {Shannan L.} and Junling Gao and Widen, {Steven G.} and Grant, {Auston C.} and Dunn, {Tiffany J.} and Azar, {Sasha R.} and Roundy, {Christopher M.} and Ying Xiong and Prusak, {Deborah J.} and Loucas, {Bradford D.} and Wood, {Thomas G.} and Yongjia Yu and Ildefonso Fern{\'a}ndez-Salas and Weaver, {Scott C.} and Nikos Vasilakis and Ping Wu",

note = "Funding Information: This work was supported in part by funds from the John S. Dunn Foundation (P.W.), the Brown Foundation of Houston (S.C.W. and N.V.), NIH grants R24AI120942 (N.V. and S.C.W.), R21AI129509-01 (P.W. and N.V.), and 4T32DA007287 (E.L.M.), and the Chief Research Office at the University of Texas Medical Branch (P.W.). Publisher Copyright: {\textcopyright} 2017 The Authors",

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doi = "10.1016/j.stemcr.2017.01.008",

language = "English (US)",

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AU - McGrath, Erica L.

AU - Rossi, Shannan L.

AU - Gao, Junling

AU - Widen, Steven G.

AU - Grant, Auston C.

AU - Dunn, Tiffany J.

AU - Azar, Sasha R.

AU - Roundy, Christopher M.

AU - Xiong, Ying

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

N1 - Funding Information: This work was supported in part by funds from the John S. Dunn Foundation (P.W.), the Brown Foundation of Houston (S.C.W. and N.V.), NIH grants R24AI120942 (N.V. and S.C.W.), R21AI129509-01 (P.W. and N.V.), and 4T32DA007287 (E.L.M.), and the Chief Research Office at the University of Texas Medical Branch (P.W.). Publisher Copyright: © 2017 The Authors

PY - 2017/3/14

Y1 - 2017/3/14

N2 - 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.

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.

KW - Zika virus

KW - astrocyte

KW - differentiation

KW - human neural stem cell

KW - innate immunity

KW - neurogenesis

KW - neuron

KW - proliferation

KW - transcriptome

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JO - Stem Cell Reports

JF - Stem Cell Reports

IS - 3

ER -

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

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Keywords

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