Contributors: Department of Neuroscience, Yale University School of Medicine; Yale School of Medicine New Haven, Connecticut (YSM); 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; 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 (IP); 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, Yale School of Medicine; Yale School of Medicine New Haven, Connecticut (YSM)-Yale School of Medicine New Haven, Connecticut (YSM); 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.
نبذة مختصرة : International audience ; Graphical Abstract Highlights d Derivation of human neocortical and spinal cord neuroepithelial stem (NES) cells d Zika virus (ZIKV) infects NES cells and radial glia, impairing mitosis and survival d ZIKV induces mitochondrial sequestration of centrosomal phospho-TBK1 d Nucleoside analogs inhibit ZIKV replication, protecting NES cells from cell death In Brief 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.
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