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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Bibliographic Details
Published in:PLoS neglected tropical diseases 2021-03, Vol.15 (3), p.e0009183-e0009183
Main Authors: 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
Format: Article
Language:English
Subjects:
Antibodies
Antiviral agents
ATP
Biology and Life Sciences
Bovine serum albumin
Brain
Brain - immunology
Brain - virology
Cell Differentiation
Cell Proliferation
Cell viability
Cells
Defence mechanisms
Development and progression
Fetuses
Gene expression
Health aspects
Horseradish peroxidase
Humans
Immune response
Immune system
Immunity
Immunity, Innate
Immunoglobulin G
Infections
Innate immunity
Interferon
Medicine and Health Sciences
Microcephaly
Nervous system diseases
Neural stem cells
Neural Stem Cells - immunology
Neural Stem Cells - virology
Neurogenesis
Neurogenesis - immunology
Nucleic acids
Peroxidase
Proteins
Receptors
Risk factors
Serum
Serum albumin
Software
Stem cell transplantation
Stem cells
TLR3 protein
Toll-like receptors
Tropical diseases
Vector-borne diseases
Viral infections
Virus Replication
Viruses
Zika virus
Zika Virus - physiology
Zika Virus Infection - immunology
Zika Virus Infection - virology
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Description
Summary: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.
ISSN:1935-2735
1935-2727
1935-2735
DOI:10.1371/journal.pntd.0009183