Zika Virus Disrupts Phospho-TBK1 Localization and Mitosis in Human Neuroepithelial Stem Cells and Radial Glia
| Autor: | Tamas L. Horvath, Maria Teresa Dell’Anno, Xiao-Bing Gao, Naoki Nakagawa, Anze Testen, Yalan Zhang, Tianliuyun Gao, Mihovil Pletikos, Candace Bichsel, Nenad Sestan, Mingfeng Li, Sirisha Pochareddy, Brett D. Lindenbach, Leonard K. Kaczmarek, Zhen Li, Wenqi Han, Forrest O. Gulden, Fuchen Liu, André M. M. Sousa, Stephen M. Strittmatter, Andrew T.N. Tebbenkamp, Marco Onorati, Steven Lisgo, Jernej Mlakar, Marie Flamand, Mara Popović, Eva S. Anton, Luis Varela, Klara Szigeti-Buck, Ying Zhu |
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| Přispěvatelé: | Department of Neuroscience [New Haven], Yale University School of Medicine-Kavli Institute for Neuroscience [New Haven], Department of Cell Biology and Physiology, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), Cellular Neuroscience, Neurodegeneration and Repair Program, Departments of Neurology and Neuroscience [New Haven], Yale University School of Medicine, Section of Comparative Medicine [New Haven], Institute of Genetic Medicine, Newcastle University [Newcastle], Departments of pharmacology and molecular biophysics and biochemistry [New Haven], University of Ljubljana, Département de Virologie - Department of Virology, Institut Pasteur [Paris], Departments of Internal Medicine, Cellular & Molecular Physiology, Departments of Medicine and Cell Biology & Physiology, Department of Microbial Pathogenesis, Reproductive Neuroscience Unit, Department of Obstetrics and Gynecology and Department of Neurobiology, Yale Program in Integrative Cell Signaling and Neurobiology of Metabolism, Kavli Institute for Neuroscience [New Haven], Departments of Psychiatry and Genetics, This work was supported by grants NS076503, MH103339, MH105972, MH106934, MH060929, NS080388, AG034924, AG047270, DC01919, AI120113, and AI089826 from the NIH, SFARI 307705 from the Simons Foundation, and 15-RMA-YALE-31 from Connecticut Innovations’ Regenerative Medicine Research Fund. The Laboratory of Developmental Biology at the University of Washington, Seattle, and Human Developmental Biology Resource were supported by NIH award number HD0008836 and the Joint MRC/Wellcome Trust grant 099175/Z/12/Z, respectively. Additional support was provided by the Kavli Foundation and the Falk Medical Research Trust., Department of Neuroscience, Yale University School of Medicine, Yale School of Medicine [New Haven, Connecticut] (YSM), Institut Pasteur [Paris] (IP), Kavli Institute for Neuroscience, Yale School of Medicine, Yale School of Medicine [New Haven, Connecticut] (YSM)-Yale School of Medicine [New Haven, Connecticut] (YSM) |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Genetics and Molecular Biology (all)
Microcephaly Transcription Genetic Neocortex MESH: Neuroepithelial Cells/ultrastructure Biochemistry environment and public health MESH: Brain/virology Neural Stem Cells MESH: Centrosome/drug effects MESH: Mitochondria/metabolism lcsh:QH301-705.5 Neurons MESH: Protein-Serine-Threonine Kinases/metabolism Zika Virus Infection Brain MESH: Neurons/virology MESH: Neural Stem Cells/virology MESH: Neural Stem Cells/immunology Nucleosides MESH: Zika Virus/physiology MESH: Virus Replication/drug effects Neural stem cell 3. Good health Cell biology Neuroepithelial cell MESH: Brain/pathology [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology Spinal Cord MESH: Neocortex/pathology MESH: Neuroepithelial Cells/immunology Neuroglia MESH: Receptor Protein-Tyrosine Kinases/metabolism Article General Biochemistry Genetics and Molecular Biology MESH: Protein Kinase Inhibitors/pharmacology 03 medical and health sciences MESH: Gene Expression Profiling Fetus Humans MESH: Phosphorylation/drug effects Mitosis MESH: Neural Stem Cells/ultrastructure Biochemistry Genetics and Molecular Biology (all) MESH: Humans Receptor Protein-Tyrosine Kinases MESH: Zika Virus/pathogenicity medicine.disease Immunity Innate MESH: Mitosis/drug effects 030104 developmental biology MESH: Neuroprotective Agents/pharmacology MESH: Mitochondria/drug effects MESH: Spinal Cord/pathology MESH: Neuroglia/ultrastructure 0301 basic medicine MESH: Fetus/virology viruses [SDV]Life Sciences [q-bio] Neuroepithelial Cells MESH: Zika Virus/ultrastructure Virus Replication MESH: Neurons/drug effects MESH: Neuroepithelial Cells/drug effects MESH: Zika Virus Infection/pathology MESH: Neurons/pathology MESH: Immunity Innate/drug effects Phosphorylation Genetics Cell Death MESH: Transcription Genetic/drug effects MESH: Neuroglia/virology MESH: Nucleosides/pharmacology Mitochondria Neuroprotective Agents MESH: Neuroglia/pathology lipids (amino acids peptides and proteins) MESH: Zika Virus Infection/virology Stem cell Programmed cell death MESH: Centrosome/metabolism MESH: Brain/embryology Protein Serine-Threonine Kinases Biology Proto-Oncogene Proteins MESH: Microcephaly/pathology medicine MESH: Zika Virus/drug effects Protein Kinase Inhibitors Centrosome MESH: Neural Stem Cells/enzymology Gene Expression Profiling MESH: Proto-Oncogene Proteins/metabolism Zika Virus Axl Receptor Tyrosine Kinase MESH: Microcephaly/virology Gene expression profiling MESH: Cell Death/drug effects lcsh:Biology (General) MESH: Neuroepithelial Cells/virology |
| Zdroj: | Cell Reports Cell Reports, Elsevier Inc, 2016, 16 (10), pp.2576-2592. ⟨10.1016/j.celrep.2016.08.038⟩ Cell Reports, 2016, 16 (10), pp.2576-2592. ⟨10.1016/j.celrep.2016.08.038⟩ Cell Reports, Vol 16, Iss 10, Pp 2576-2592 (2016) |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2016.08.038⟩ |
| Popis: | SummaryThe 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. |
| Databáze: | OpenAIRE |
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