Language:

Zika Virus Disrupts Phospho-TBK1 Localization and Mitosis in Human Neuroepithelial Stem Cells and Radial Glia

Cell reports (Cambridge), 2016-09, Vol.16 (10), p.2576-2592 [Peer Reviewed Journal]

2016 The Authors ;Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved. ;Attribution - NonCommercial - NoDerivatives ;ISSN: 2211-1247 ;EISSN: 2211-1247 ;DOI: 10.1016/j.celrep.2016.08.038 ;PMID: 27568284

Full text available

Citations Cited by

Actions
1. Add to My Research
2. Remove from My Research
3. E-mail
4. Print
5. Permalink
6. Citation
7. EasyBib
8. EndNote
9. RefWorks
10. Delicious
11. Export RIS
12. Export BibTeX

Title:
Zika Virus Disrupts Phospho-TBK1 Localization and Mitosis in Human Neuroepithelial Stem Cells and Radial Glia
Author: Onorati, Marco ; Li, Zhen ; Liu, Fuchen ; Sousa, André M.M. ; Nakagawa, Naoki ; Li, Mingfeng ; Dell’Anno, Maria Teresa ; Gulden, Forrest O. ; Pochareddy, Sirisha ; Tebbenkamp, Andrew T.N. ; Han, Wenqi ; Pletikos, Mihovil ; Gao, Tianliuyun ; Zhu, Ying ; Bichsel, Candace ; Varela, Luis ; Szigeti-Buck, Klara ; Lisgo, Steven ; Zhang, Yalan ; Testen, Anze ; Gao, Xiao-Bing ; Mlakar, Jernej ; Popovic, Mara ; Flamand, Marie ; Strittmatter, Stephen M. ; Kaczmarek, Leonard K. ; Anton, E.S. ; Horvath, Tamas L. ; Lindenbach, Brett D. ; Sestan, Nenad
Subjects: Brain - embryology ; Brain - pathology ; Brain - virology ; Cell Death - drug effects ; Centrosome - drug effects ; Centrosome - metabolism ; Fetus - virology ; Gene Expression Profiling ; Humans ; Immunity, Innate - drug effects ; Life Sciences ; Microbiology and Parasitology ; Microcephaly - pathology ; Microcephaly - virology ; Mitochondria - drug effects ; Mitochondria - metabolism ; Mitosis - drug effects ; Neocortex - pathology ; Neural Stem Cells - enzymology ; Neural Stem Cells - immunology ; Neural Stem Cells - ultrastructure ; Neural Stem Cells - virology ; Neuroepithelial Cells - drug effects ; Neuroepithelial Cells - immunology ; Neuroepithelial Cells - ultrastructure ; Neuroepithelial Cells - virology ; Neuroglia - pathology ; Neuroglia - ultrastructure ; Neuroglia - virology ; Neurons - drug effects ; Neurons - pathology ; Neurons - virology ; Neuroprotective Agents - pharmacology ; Nucleosides - pharmacology ; Phosphorylation - drug effects ; Protein Kinase Inhibitors - pharmacology ; Protein Serine-Threonine Kinases - metabolism ; Proto-Oncogene Proteins - metabolism ; Receptor Protein-Tyrosine Kinases - metabolism ; Spinal Cord - pathology ; Transcription, Genetic - drug effects ; Virus Replication - drug effects ; Zika Virus - drug effects ; Zika Virus - pathogenicity ; Zika Virus - physiology ; Zika Virus - ultrastructure ; Zika Virus Infection - pathology ; Zika Virus Infection - virology
Is Part Of: Cell reports (Cambridge), 2016-09, Vol.16 (10), p.2576-2592
Description: The mechanisms underlying Zika virus (ZIKV)-related microcephaly and other neurodevelopment defects remain poorly understood. Here, we describe the derivation and characterization, including single-cell RNA-seq, of neocortical and spinal cord neuroepithelial stem (NES) cells to model early human neurodevelopment and ZIKV-related neuropathogenesis. By analyzing human NES cells, organotypic fetal brain slices, and a ZIKV-infected micrencephalic brain, we show that ZIKV infects both neocortical and spinal NES cells as well as their fetal homolog, radial glial cells (RGCs), causing disrupted mitoses, supernumerary centrosomes, structural disorganization, and cell death. ZIKV infection of NES cells and RGCs causes centrosomal depletion and mitochondrial sequestration of phospho-TBK1 during mitosis. We also found that nucleoside analogs inhibit ZIKV replication in NES cells, protecting them from ZIKV-induced pTBK1 relocalization and cell death. We established a model system of human neural stem cells to reveal cellular and molecular mechanisms underlying neurodevelopmental defects associated with ZIKV infection and its potential treatment. [Display omitted] •Derivation of human neocortical and spinal cord neuroepithelial stem (NES) cells•Zika virus (ZIKV) infects NES cells and radial glia, impairing mitosis and survival•ZIKV induces mitochondrial sequestration of centrosomal phospho-TBK1•Nucleoside analogs inhibit ZIKV replication, protecting NES cells from cell death Onorati et al. establish neuroepithelial stem (NES) cells as a model for studying human neurodevelopment and ZIKV-induced microcephaly. Together with analyses in human brain slices and microcephalic human fetal tissue, they find that ZIKV predominantly infects NES and radial glial cells, reveal a pivotal role for pTBK1, and find that nucleoside analogs inhibit ZIKV replication, protecting NES cells from cell death.
Publisher: United States: Elsevier Inc
Language: English
Identifier: ISSN: 2211-1247
EISSN: 2211-1247
DOI: 10.1016/j.celrep.2016.08.038
PMID: 27568284
Source: Cell Press Free Archives
Geneva Foundation Free Medical Journals at publisher websites
Hyper Article en Ligne (HAL) (Open Access)
MEDLINE
DOAJ Directory of Open Access Journals

Back to results list


INSPIRE LIBRARY - TON DUC THANG UNIVERSITY	(84-028) 37 755 057	Feedback
19 Nguyen Huu Tho St. Dist.7, HCM	thuvien@tdtu.edu.vn	Feedback

Zika Virus Disrupts Phospho-TBK1 Localization and Mitosis in Human Neuroepithelial Stem Cells and Radial Glia

2016 The Authors ;Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved. ;Attribution - NonCommercial - NoDerivatives ;ISSN: 2211-1247 ;EISSN: 2211-1247 ;DOI: 10.1016/j.celrep.2016.08.038 ;PMID: 27568284

Searching Remote Databases, Please Wait