Inhibition of innate immune response ameliorates zika virus-induced neurogenesis deficit in human neural stem cells

Pei Xu; Junling Gao; Chao Shan; Tiffany J. Dunn; Xuping Xie; Hongjie Xia; Jing Zou; Beatriz H. Thames; Amulya Sajja; Yongjia Yu; Alexander N. Freiberg; Nikos Vasilakis; Pei-Yong Shi; Scott C. Weaver; Ping Wu

doi:10.1371/journal.pntd.0009183

Inhibition of innate immune response ameliorates zika virus-induced neurogenesis deficit in human neural stem cells

Pei Xu, Junling Gao, Chao Shan, Tiffany J. Dunn, Xuping Xie, Hongjie Xia, Jing Zou, Beatriz H. Thames, Amulya Sajja, Yongjia Yu, Alexander N. Freiberg, Nikos Vasilakis, Pei-Yong Shi, Scott C. Weaver, Ping Wu

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Abstract

Global Zika virus (ZIKV) outbreaks and their strong link to microcephaly have raised major public health concerns. ZIKV has been reported to affect the innate immune responses in neural stem/progenitor cells (NS/PCs). However, it is unclear how these immune factors affect neurogenesis. In this study, we used Asian-American lineage ZIKV strain PRVABC59 to infect primary human NS/PCs originally derived from fetal brains. We found that ZIKV overactivated key molecules in the innate immune pathways to impair neurogenesis in a cell stage-dependent manner. Inhibiting the overactivated innate immune responses amelio-rated ZIKV-induced neurogenesis reduction. This study thus suggests that orchestrating the host innate immune responses in NS/PCs after ZIKV infection could be promising therapeu-tic approach to attenuate ZIKV-associated neuropathology.

Original language	English (US)
Article number	e0009183
Journal	PLoS neglected tropical diseases
Volume	15
Issue number	3
DOIs	https://doi.org/10.1371/journal.pntd.0009183
State	Published - Mar 2021

ASJC Scopus subject areas

Public Health, Environmental and Occupational Health
Infectious Diseases

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Xu, P., Gao, J., Shan, C., Dunn, T. J., Xie, X., Xia, H., Zou, J., Thames, B. H., Sajja, A., Yu, Y., Freiberg, A. N., Vasilakis, N., Shi, P.-Y., Weaver, S. C., & Wu, P. (2021). Inhibition of innate immune response ameliorates zika virus-induced neurogenesis deficit in human neural stem cells. PLoS neglected tropical diseases, 15(3), Article e0009183. https://doi.org/10.1371/journal.pntd.0009183

Xu, P, Gao, J, Shan, C, Dunn, TJ, Xie, X, Xia, H, Zou, J, Thames, BH, Sajja, A, Yu, Y , Freiberg, AN , Vasilakis, N, Shi, P-Y, Weaver, SC & Wu, P 2021, 'Inhibition of innate immune response ameliorates zika virus-induced neurogenesis deficit in human neural stem cells', PLoS neglected tropical diseases, vol. 15, no. 3, e0009183. https://doi.org/10.1371/journal.pntd.0009183

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abstract = "Global Zika virus (ZIKV) outbreaks and their strong link to microcephaly have raised major public health concerns. ZIKV has been reported to affect the innate immune responses in neural stem/progenitor cells (NS/PCs). However, it is unclear how these immune factors affect neurogenesis. In this study, we used Asian-American lineage ZIKV strain PRVABC59 to infect primary human NS/PCs originally derived from fetal brains. We found that ZIKV overactivated key molecules in the innate immune pathways to impair neurogenesis in a cell stage-dependent manner. Inhibiting the overactivated innate immune responses amelio-rated ZIKV-induced neurogenesis reduction. This study thus suggests that orchestrating the host innate immune responses in NS/PCs after ZIKV infection could be promising therapeu-tic approach to attenuate ZIKV-associated neuropathology.",

author = "Pei Xu and Junling Gao and Chao Shan and Dunn, {Tiffany J.} and Xuping Xie and Hongjie Xia and Jing Zou and Thames, {Beatriz H.} and Amulya Sajja and Yongjia Yu and Freiberg, {Alexander N.} and Nikos Vasilakis and Pei-Yong Shi and Weaver, {Scott C.} and Ping Wu",

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AU - Thames, Beatriz H.

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AU - Freiberg, Alexander N.

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Inhibition of innate immune response ameliorates zika virus-induced neurogenesis deficit in human neural stem cells

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