ArticleCell death and differentiation2018
Zika virus E protein alters the properties of human fetal neural stem cells by modulating microRNA circuitry.
Article in Cell death and differentiation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 49 citations in OpenAlex.
- ZIKV envelope protein is a strong blocker of early directional differentiation in the neural lineage.Communications biology · 2026Article
- Intrauterine Zika Virus Infection: An Overview of the Current Findings.Journal of personalized medicine · 2025Review
- Interplay Between Zika Virus-Induced Autophagy and Neural Stem Cell Fate Determination.Molecular neurobiology · 2024Article
- Regulation of Onecut2 by miR-9-5p in Japanese encephalitis virus infected neural stem/progenitor cells.Microbiology spectrum · 2024Article
- Review
- Congenital Zika Virus Syndrome: Microcephaly and Orofacial Anomalies.Life (Basel, Switzerland) · 2023Review
- Insights into Zika Virus Pathogenesis and Potential Therapeutic Strategies.Biomedicines · 2023Review
- Strain Variation Can Significantly Modulate the miRNA Response to Zika Virus Infection.International journal of molecular sciences · 2023Article
- Hypoxia Induces Early Neurogenesis in Human Fetal Neural Stem Cells by Activating the WNT Pathway.Molecular neurobiology · 2023Article
- Zika virus E protein modulates functions of human brain microvascular endothelial cells and astrocytes: implications on blood-brain barrier properties.Frontiers in cellular neuroscience · 2023Article
- Zika virus as an emerging arbovirus of international public health concern.Osong public health and research perspectives · 2022Article
- microRNAs Control Antiviral Immune Response, Cell Death and Chemotaxis Pathways in Human Neuronal Precursor Cells (NPCs) during Zika Virus Infection.International journal of molecular sciences · 2022Article
- Identification of novel lncRNA by reanalysis of RNA-seq data in Zika Virus Infected hiNPCs.Virusdisease · 2022Article
- Copper dependent ERK1/2 phosphorylation is essential for the viability of neurons and not glia.Metallomics : integrated biometal science · 2022Article
- Regulatory Role of Host MicroRNAs in Flaviviruses Infection.Frontiers in microbiology · 2022Review
- Involvement of host microRNAs in flavivirus-induced neuropathology: An update.Journal of biosciences · 2022Review
- Review
- Are the Organoid Models an Invaluable Contribution to ZIKA Virus Research?Pathogens (Basel, Switzerland) · 2021Review
- Inter-regulatory role of microRNAs in interaction between viruses and stem cells.World journal of stem cells · 2021Review
- Molecular mechanisms of zika virus pathogenesis: An update.The Indian journal of medical research · 2021Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Zika virus (ZV) infects neural stem cells (NSCs) and causes quiescence in NSCs, reducing the pool of brain cells, leading to microcephaly. Despite conscientious efforts, the molecular mechanisms for ZV-mediated effects on NSCs lack clarity. This study aimed to explore the underlying mechanisms for ZV-mediated induction of quiescence in the primary cultures of human fetal neural stem cells (fNSCs). We demonstrate that expression of ZV envelope (E) protein displays maximum quiescence in human fNSCs by accumulating cells in the G0/G1 phase of the cell cycle as compared to other non-structural proteins, viz. NS2A, NS4A and NS4B. E protein induces immature differentiation by induction of pro-neuronal genes in proliferating fNSCs, induces apoptosis in differentiating fNSCs 3 days post differentiation, and disrupts migration of cells from differentiating neurospheres. In utero electroporation of mouse brain with E protein shows drastic downregulation of proliferating cells in ventricular and subventricular zone regions. Global microRNA sequencing suggests that E protein modulates miRNA circuitry. Among differentially expressed miRNAs, we found 14 upregulated and 11 downregulated miRNAs. Mir-204-3p and mir-1273g-3p directly regulate NOTCH2 and PAX3 expression, respectively, by binding to their 3'UTR. Bioinformatic analysis using GO analysis for the targets of differentially expressed miRNAs revealed enrichment of cell cycle and developmental processes. Furthermore, WNT, CCKR, PDGF, EGF, p53, and NOTCH signaling pathways were among the top enriched pathways. Thus, our study provides evidence for the involvement of ZV E protein and novel insights into the molecular mechanism through identification of miRNA circuitry. Art work depicting the effect of Zika virus E protein on human fetal neural stem cells.
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