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

Marco Onorati 1 Zhen Li 1 Fuchen Liu 1 André m. M. Sousa 1 Naoki Nakagawa 2 Mingfeng Li 1 Maria teresa Dell’anno 3 Forrest o. Gulden 1 Sirisha Pochareddy 1 Andrew t.N. Tebbenkamp 1 Wenqi Han 1 Mihovil Pletikos 1 Tianliuyun Gao 1 ying Zhu 1 Candace Bichsel 1 Luis Varela 4 Klara Szigeti-Buck 4 Steven Lisgo 5 yalan Zhang 6 Anze Testen 2 Xiao-Bing Gao 4 Jernej Mlakar 7 Mara Popovic 7 Marie Flamand 8 Stephen m. Strittmatter 3 Leonard k. Kaczmarek 6, 9 E.S. Anton 10 Tamas l. Horvath 11, 12, 13, 4 Brett d. Lindenbach 11 Nenad Sestan 14, 3, 4, 15 
Abstract : 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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Marco Onorati, Zhen Li, Fuchen Liu, André m. M. Sousa, Naoki Nakagawa, et al.. Zika Virus Disrupts Phospho-TBK1 Localization and Mitosis in Human Neuroepithelial Stem Cells and Radial Glia. Cell Reports, Elsevier Inc, 2016, 16 (10), pp.2576-2592. ⟨10.1016/j.celrep.2016.08.038⟩. ⟨pasteur-01739212⟩

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