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)

1 Department of Neuroscience, Yale University School of Medicine
2 Department of Cell Biology and Physiology
3 Cellular Neuroscience, Neurodegeneration and Repair Program, Departments of Neurology and Neuroscience [New Haven]
4 Section of Comparative Medicine [New Haven]
5 Institute of Genetic Medicine
6 Departments of pharmacology and molecular biophysics and biochemistry [New Haven]
7 University of Ljubljana
8 Département de Virologie - Department of Virology
9 Departments of Internal Medicine, Cellular & Molecular Physiology
10 Departments of Medicine and Cell Biology & Physiology
11 Department of Microbial Pathogenesis
12 Reproductive Neuroscience Unit, Department of Obstetrics and Gynecology and Department of Neurobiology
13 Yale Program in Integrative Cell Signaling and Neurobiology of Metabolism
14 Kavli Institute for Neuroscience, Yale School of Medicine
15 Departments of Psychiatry and Genetics

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.

Domaines: Sciences du Vivant [q-bio]; Microbiologie et Parasitologie

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, 2016, 16 (10), pp.2576-2592. ⟨10.1016/j.celrep.2016.08.038⟩. ⟨pasteur-01739212⟩