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

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...

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Autores principales: Xu, Pei, Gao, Junling, Shan, Chao, Dunn, Tiffany J., Xie, Xuping, Xia, Hongjie, Zou, Jing, Thames, Beatriz H., Sajja, Amulya, Yu, Yongjia, Freiberg, Alexander N., Vasilakis, Nikos, Shi, Pei-Yong, Weaver, Scott C., Wu, Ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959377/
https://www.ncbi.nlm.nih.gov/pubmed/33657175
http://dx.doi.org/10.1371/journal.pntd.0009183
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author Xu, Pei
Gao, Junling
Shan, Chao
Dunn, Tiffany J.
Xie, Xuping
Xia, Hongjie
Zou, Jing
Thames, Beatriz H.
Sajja, Amulya
Yu, Yongjia
Freiberg, Alexander N.
Vasilakis, Nikos
Shi, Pei-Yong
Weaver, Scott C.
Wu, Ping
author_facet Xu, Pei
Gao, Junling
Shan, Chao
Dunn, Tiffany J.
Xie, Xuping
Xia, Hongjie
Zou, Jing
Thames, Beatriz H.
Sajja, Amulya
Yu, Yongjia
Freiberg, Alexander N.
Vasilakis, Nikos
Shi, Pei-Yong
Weaver, Scott C.
Wu, Ping
author_sort Xu, Pei
collection PubMed
description 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 ameliorated ZIKV-induced neurogenesis reduction. This study thus suggests that orchestrating the host innate immune responses in NS/PCs after ZIKV infection could be promising therapeutic approach to attenuate ZIKV-associated neuropathology.
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spelling pubmed-79593772021-03-25 Inhibition of innate immune response ameliorates Zika virus-induced neurogenesis deficit in human neural stem cells Xu, Pei Gao, Junling Shan, Chao Dunn, Tiffany J. Xie, Xuping Xia, Hongjie Zou, Jing Thames, Beatriz H. Sajja, Amulya Yu, Yongjia Freiberg, Alexander N. Vasilakis, Nikos Shi, Pei-Yong Weaver, Scott C. Wu, Ping PLoS Negl Trop Dis Research Article 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 ameliorated ZIKV-induced neurogenesis reduction. This study thus suggests that orchestrating the host innate immune responses in NS/PCs after ZIKV infection could be promising therapeutic approach to attenuate ZIKV-associated neuropathology. Public Library of Science 2021-03-03 /pmc/articles/PMC7959377/ /pubmed/33657175 http://dx.doi.org/10.1371/journal.pntd.0009183 Text en © 2021 Xu et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Xu, Pei
Gao, Junling
Shan, Chao
Dunn, Tiffany J.
Xie, Xuping
Xia, Hongjie
Zou, Jing
Thames, Beatriz H.
Sajja, Amulya
Yu, Yongjia
Freiberg, Alexander N.
Vasilakis, Nikos
Shi, Pei-Yong
Weaver, Scott C.
Wu, Ping
Inhibition of innate immune response ameliorates Zika virus-induced neurogenesis deficit in human neural stem cells
title Inhibition of innate immune response ameliorates Zika virus-induced neurogenesis deficit in human neural stem cells
title_full Inhibition of innate immune response ameliorates Zika virus-induced neurogenesis deficit in human neural stem cells
title_fullStr Inhibition of innate immune response ameliorates Zika virus-induced neurogenesis deficit in human neural stem cells
title_full_unstemmed Inhibition of innate immune response ameliorates Zika virus-induced neurogenesis deficit in human neural stem cells
title_short Inhibition of innate immune response ameliorates Zika virus-induced neurogenesis deficit in human neural stem cells
title_sort inhibition of innate immune response ameliorates zika virus-induced neurogenesis deficit in human neural stem cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959377/
https://www.ncbi.nlm.nih.gov/pubmed/33657175
http://dx.doi.org/10.1371/journal.pntd.0009183
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