scholarly journals Dysregulation of Ephrin receptor and PPAR signaling pathways in neural progenitor cells infected by Zika virus

2020 ◽  
Vol 9 (1) ◽  
pp. 2046-2060
Author(s):  
Sathya N. Thulasi Raman ◽  
Elyse Latreille ◽  
Jun Gao ◽  
Wanyue Zhang ◽  
Jianguo Wu ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Progenitor Cells ◽  
Zika Virus ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
Ephrin Receptor ◽  
Ppar Signaling

scholarly journals Zika virus is transmitted in neural progenitor cells via cell-to-cell spread and infection is inhibited by the autophagy inducer trehalose

2020 ◽  
pp. JVI.02024-20
Author(s):  
Alex E Clark ◽  
Zhe Zhu ◽  
Florian Krach ◽  
Jeremy N Rich ◽  
Gene W. Yeo ◽  
...  
Keyword(s):  
Viral Replication ◽  
Progenitor Cells ◽  
Zika Virus ◽  
Neural Progenitor Cells ◽  
Neutralizing Antibody ◽  
Neural Progenitor ◽  
Health Concern ◽  
Free Virus ◽  
Zikv Infection ◽  
Infected Cells

Zika virus (ZIKV) is a mosquito-borne human pathogen that causes congenital Zika syndrome and neurological symptoms in some adults. There are currently no approved treatments or vaccines for ZIKV, and exploration of therapies targeting host processes could avoid viral development of drug resistance. The purpose of our study was to determine if the non-toxic and widely used disaccharide trehalose, which showed antiviral activity against Human Cytomegalovirus (HCMV) in our previous work, could restrict ZIKV infection in clinically relevant neural progenitor cells (NPCs). Trehalose is known to induce autophagy, the degradation and recycling of cellular components. Whether autophagy is proviral or antiviral for ZIKV is controversial and depends on cell type and specific conditions used to activate or inhibit autophagy. We show here that trehalose treatment of NPCs infected with recent ZIKV isolates from Panama and Puerto Rico significantly reduces viral replication and spread. In addition, we demonstrate that ZIKV infection in NPCs spreads primarily cell-to-cell as an expanding infectious center, and NPCs are infected via contact with infected cells far more efficiently than by cell-free virus. Importantly, ZIKV was able to spread in NPCs in the presence of neutralizing antibody.Importance Zika virus causes birth defects and can lead to neurological disease in adults. While infection rates are currently low, ZIKV remains a public health concern with no treatment or vaccine available. Targeting a cellular pathway to inhibit viral replication is a potential treatment strategy that avoids development of antiviral resistance. We demonstrate in this study that the non-toxic autophagy-inducing disaccharide trehalose reduces spread and output of ZIKV in infected neural progenitor cells (NPCs), the major cells infected in the fetus. We show that ZIKV spreads cell-to-cell in NPCs as an infectious center and that NPCs are more permissive to infection by contact with infected cells than by cell-free virus. We find that neutralizing antibody does not prevent the spread of the infection in NPCs. These results are significant in demonstrating anti-ZIKV activity of trehalose and in clarifying the primary means of Zika virus spread in clinically relevant target cells.

scholarly journals Anti-Zika virus RNAi in neural progenitor cells

Cell Research ◽  
2019 ◽  
Vol 29 (4) ◽  
pp. 261-262 ◽  
Author(s):  
Xuping Xie ◽  
Pei-Yong Shi
Keyword(s):  
Progenitor Cells ◽  
Zika Virus ◽  
Neural Progenitor Cells ◽  
Neural Progenitor

scholarly journals Genome-wide screens in accelerated human stem cell-derived neural progenitor cells identify Zika virus host factors and drivers of proliferation

2018 ◽  
Author(s):  
Michael F. Wells ◽  
Max R. Salick ◽  
Federica Piccioni ◽  
Ellen J. Hill ◽  
Jana M. Mitchell ◽  
...  
Keyword(s):  
Stem Cell ◽  
Progenitor Cells ◽  
Zika Virus ◽  
Large Scale ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
Autism Spectrum ◽  
Host Factors ◽  
Protein Markers ◽  
Genome Wide

SUMMARYNeural progenitor cells (NPCs) are essential to brain development and their dysfunction is linked to several disorders, including autism, Zika Virus Congenital Syndrome, and cancer. Understanding of these conditions has been improved by advancements with stem cell-derived NPC models. However, current differentiation methods require many days or weeks to generate NPCs and show variability in efficacy among cell lines. Here, we describe humanStem cell-derivedNGN2-acceleratedProgenitor cells (SNaPs), which are produced in only 48 hours. SNaPs express canonical forebrain NPC protein markers, are proliferative, multipotent, and like other human NPCs, are susceptible to Zika-mediated death. We further demonstrate SNaPs are valuable for large-scale investigations of genetic and environmental influencers of neurodevelopment by deploying them for genome-wide CRISPR-Cas9 screens. Our studies expand knowledge of NPCs by identifying known and novel Zika host factors, as well as new regulators of NPC proliferation validated by re-identification of the autism spectrum genePTEN.

Zika virus alters DNA methylation status of genes involved in Hippo signaling pathway in human neural progenitor cells

Epigenomics ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1143-1161 ◽  
Author(s):  
Deepika Kandilya ◽  
Silambarasan Maskomani ◽  
Sukanya Shyamasundar ◽  
Paul Anantharajah Tambyah ◽  
Chan Shiao Yng ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Progenitor Cells ◽  
Signaling Pathway ◽  
Zika Virus ◽  
Neural Progenitor Cells ◽  
Methylation Status ◽  
Neural Progenitor ◽  
Hippo Signaling ◽  
Hippo Signaling Pathway ◽  
Human Neural Progenitor Cells

Aim: This study was aimed to understand if Zika virus (ZIKV) alters the DNA methylome of human neural progenitor cells (hNPCs). Materials & methods: Whole genome DNA methylation profiling was performed using human methylationEPIC array in control and ZIKV infected hNPCs. Results & conclusion: ZIKV infection altered the DNA methylation of several genes such as WWTR1 (TAZ) and RASSF1 of Hippo signaling pathway which regulates organ size during brain development, and decreased the expression of several centrosomal-related microcephaly genes, and genes involved in stemness and differentiation in human neural progenitor cells. Overall, ZIKV downregulated the Hippo signaling pathway genes which perturb the stemness and differentiation process in hNPCs, which could form the basis for ZIKV-induced microcephaly.

scholarly journals In Vitro Zika Virus Infection of Human Neural Progenitor Cells: Meta-Analysis of RNA-Seq Assays

2020 ◽  
Vol 8 (2) ◽  
pp. 270 ◽  
Author(s):  
Rossella Gratton ◽  
Paola Maura Tricarico ◽  
Almerinda Agrelli ◽  
Heverton Valentim Colaço da Silva ◽  
Lucas Coêlho Bernardo ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Zika Virus ◽  
Neural Progenitor Cells ◽  
Meta Analysis ◽  
Fetal Brain ◽  
Neural Progenitor ◽  
Gene Expression Omnibus ◽  
Human Neural Progenitor Cells ◽  
Apoptosis Pathways

The Zika virus (ZIKV) is an emergent arthropod-borne virus (arbovirus) responsible for congenital Zika syndrome (CZS) and a range of other congenital malformations. Evidence shows that ZIKV infects human neural progenitor cells (hNPCs) in the fetal brain, prompting inflammation and tissue damage/loss. Despite recent advances, little is known about the pathways involved in CZS pathogenesis. We performed a meta-analysis, gene ontology (GO), and pathway analysis of whole transcriptome studies with the aim of clarifying the genes and pathways potentially altered during hNPCs infection with ZIKV. We selected three studies (17 samples of infected hPNCs compared to hPNCs uninfected controls) through a systematic search of the Gene Expression Omnibus (GEO) database. The raw reads were trimmed, counted, and normalized. Next, we performed a rank product meta-analysis to detect consistently differentially expressed genes (DEGs) in these independent experiments. We detected 13 statistically significant DEGs. GO ontology and reactome analysis showed an enrichment of interferon, pro-inflammatory, and chemokines signaling and apoptosis pathways in ZIKV-infected cells. Moreover, we detected three possible new candidate genes involved in hNPCs infection: APOL6, XAF1, and TNFRSF1. Our results confirm that interferon (IFN) signaling dominates the ZIKV response, and that a crucial contribution is given by apoptotic pathways, which might elicit the CZS phenotype.

scholarly journals Heparin prevents Zika virus induced-cytopathic effects in human neural progenitor cells

2017 ◽  
Vol 140 ◽  
pp. 13-17 ◽  
Author(s):  
Silvia Ghezzi ◽  
Lynsay Cooper ◽  
Alicia Rubio ◽  
Isabel Pagani ◽  
Maria Rosaria Capobianchi ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Zika Virus ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
Cytopathic Effects ◽  
Human Neural Progenitor Cells

scholarly journals Natural variation in gene expression and Zika virus susceptibility revealed by villages of neural progenitor cells

2021 ◽  
Author(s):  
Michael F Wells ◽  
James Nemesh ◽  
Sulagna Ghosh ◽  
Jana M Mitchell ◽  
Curtis J Mello ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Progenitor Cells ◽  
Zika Virus ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
Virus Infectivity ◽  
Cellular Mechanisms ◽  
Natural Genetic Variation ◽  
The Impact

Variation in the human genome contributes to abundant diversity in human traits and vulnerabilities, but the underlying molecular and cellular mechanisms are not yet known, and will need scalable approaches to accelerate their recognition. Here, we advanced and applied an experimental platform that analyzes genetic, molecular, and phenotypic heterogeneity across cells from very many human donors cultured in a single, shared in vitro environment, with algorithms (Dropulation and Census-seq) for assigning phenotypes to individual donors. We used natural genetic variation and synthetic (CRISPR-Cas9) genetic perturbations to analyze the vulnerability of neural progenitor cells to infection with Zika virus. These analyses identified a common variant in the antiviral IFITM3 gene that regulated IFITM3 expression and explained most inter-individual variation in NPCs' susceptibility to Zika virus infectivity. These and other approaches could provide scalable ways to recognize the impact of genes and genetic variation on cellular phenotypes.

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