scholarly journals Zika Virus and Neuropathogenesis: The Unanswered Question of Which Strain Is More Prone to Causing Microcephaly and Other Neurological Defects

2021 ◽  
Vol 15 ◽  
Author(s):  
Emily Louise King ◽  
Nerea Irigoyen
Keyword(s):  
Cerebral Cortex ◽  
Progenitor Cells ◽  
Zika Virus ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
French Polynesia ◽  
Cellular Processes ◽  
Neurotropic Viruses ◽  
Congenital Zika Syndrome ◽  
Induced Apoptosis

Despite being perceived to be a relatively innocuous pathogen during its circulation in Africa in the 20th century, consequent outbreaks in French Polynesia and Latin America revealed the Zika virus (ZIKV) to be capable of causing severe neurological defects. Foetuses infected with the virus during pregnancy developed a range of pathologies including microcephaly, cerebral calcifications and macular scarring. These are now collectively known as Congenital Zika syndrome (CZS). It has been established that the neuropathogenesis of ZIKV results from infection of neural progenitor cells in the developing cerebral cortex. Following this, two main hypotheses have emerged: the virus causes either apoptosis or premature differentiation of neural progenitor cells, reducing the final number of mature neurons in the cerebral cortex. This review describes the cellular processes which could potentially cause virus induced apoptosis or premature differentiation, leading to speculation that a combination of the two may be responsible for the pathologies associated with ZIKV. The review also discusses which specific lineages of the ZIKV can employ these mechanisms. It has been unclear in the past whether the virus evolved its neurotropic capability following circulation in Africa, or if the virus has always caused microcephaly but public health surveillance in Africa had failed to detect it. Understanding the true neuropathogenesis of ZIKV is key to being prepared for further outbreaks in the future, and it will also provide insight into how neurotropic viruses can cause profound and life-long neurological defects.

scholarly journals Strain-Dependent Consequences of Zika Virus Infection and Differential Impact on Neural Development

Viruses ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 550 ◽  
Author(s):  
Forrest Goodfellow ◽  
Katherine Willard ◽  
Xian Wu ◽  
Shelley Scoville ◽  
Steven Stice ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Neural Development ◽  
Zika Virus ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
Experimental Models ◽  
Neurological Dysfunction ◽  
Congenital Zika Syndrome ◽  
Extensive Cell ◽  
And Migration

Maternal infection with Zika virus (ZIKV) during pregnancy can result in neonatal abnormalities, including neurological dysfunction and microcephaly. Experimental models of congenital Zika syndrome identified neural progenitor cells as a target of viral infection. Neural progenitor cells are responsible for populating the developing central nervous system with neurons and glia. Neural progenitor dysfunction can lead to severe birth defects, namely, lissencephaly, microcephaly, and cognitive deficits. For this study, the consequences of ZIKV infection in human pluripotent stem cell-derived neural progenitor (hNP) cells and neurons were evaluated. ZIKV isolates from Asian and African lineages displayed lineage-specific replication kinetics, cytopathic effects, and impacts on hNP function and neuronal differentiation. The currently circulating ZIKV isolates exhibit a unique profile of virulence, cytopathic effect, and impaired cellular functions that likely contribute to the pathological mechanism of congenital Zika syndrome. The authors found that infection with Asian-lineage ZIKV isolates impaired the proliferation and migration of hNP cells, and neuron maturation. In contrast, the African-lineage infections resulted in abrupt and extensive cell death. This work furthers the understanding of ZIKV-induced brain pathology.

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 Mammalian Fat and Dachsous cadherins regulate apical membrane organization in the embryonic cerebral cortex

2009 ◽  
Vol 185 (6) ◽  
pp. 959-967 ◽  
Author(s):  
Takashi Ishiuchi ◽  
Kazuyo Misaki ◽  
Shigenobu Yonemura ◽  
Masatoshi Takeichi ◽  
Takuji Tanoue
Keyword(s):  
Cerebral Cortex ◽  
Plasma Membrane ◽  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Apical Membrane ◽  
Neural Progenitor ◽  
Apical Plasma Membrane ◽  
Cell Contact ◽  
Membrane Organization ◽  
A Cell

Compartmentalization of the plasma membrane in a cell is fundamental for its proper functions. In this study, we present evidence that mammalian Fat4 and Dachsous1 cadherins regulate the apical plasma membrane organization in the embryonic cerebral cortex. In neural progenitor cells of the cortex, Fat4 and Dachsous1 were concentrated together in a cell–cell contact area positioned more apically than the adherens junction (AJ). These molecules interacted in a heterophilic fashion, affecting their respective protein levels. We further found that Fat4 associated and colocalized with the Pals1 complex. Ultrastructurally, the apical junctions of the progenitor cells comprised the AJ and a stretch of plasma membrane apposition extending apically from the AJ, which positionally corresponded to the Fat4–Dachsous1-positive zone. Depletion of Fat4 or Pals1 abolished this membrane apposition. These results highlight the importance of the Fat4–Dachsous1–Pals1 complex in organizing the apical membrane architecture of neural progenitor cells.

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.

scholarly journals Discordant congenital Zika syndrome twins show differential in vitro viral susceptibility of neural progenitor cells

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Luiz Carlos Caires-Júnior ◽  
Ernesto Goulart ◽  
Uirá Souto Melo ◽  
Bruno Henrique Silva Araujo ◽  
Lucas Alvizi ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
Viral Susceptibility ◽  
Congenital Zika Syndrome

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 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
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