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Zika-Virus-Encoded NS2A Disrupts Mammalian Cortical Neurogenesis by Degrading Adherens Junction Proteins.

Title: Zika-Virus-Encoded NS2A Disrupts Mammalian Cortical Neurogenesis by Degrading Adherens Junction Proteins.
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Name(s): Yoon, Ki-Jun, author
Song, Guang, author
Qian, Xuyu, author
Pan, Jianbo, author
Xu, Dan, author
Rho, Hee-Sool, author
Kim, Nam-Shik, author
Habela, Christa, author
Zheng, Lily, author
Jacob, Fadi, author
Zhang, Feiran, author
Lee, Emily M, author
Huang, Wei-Kai, author
Ringeling, Francisca Rojas, author
Vissers, Caroline, author
Li, Cui, author
Yuan, Ling, author
Kang, Koeun, author
Kim, Sunghan, author
Yeo, Junghoon, author
Cheng, Yichen, author
Liu, Sheng, author
Wen, Zhexing, author
Qin, Cheng-Feng, author
Wu, Qingfeng, author
Christian, Kimberly M, author
Tang, Hengli, author
Jin, Peng, author
Xu, Zhiheng, author
Qian, Jiang, author
Zhu, Heng, author
Song, Hongjun, author
Ming, Guo-Li, author
Type of Resource: text
Genre: Journal Article
Text
Date Issued: 2017-09-07
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: Zika virus (ZIKV) directly infects neural progenitors and impairs their proliferation. How ZIKV interacts with the host molecular machinery to impact neurogenesis in vivo is not well understood. Here, by systematically introducing individual proteins encoded by ZIKV into the embryonic mouse cortex, we show that expression of ZIKV-NS2A, but not Dengue virus (DENV)-NS2A, leads to reduced proliferation and premature differentiation of radial glial cells and aberrant positioning of newborn neurons. Mechanistically, in vitro mapping of protein-interactomes and biochemical analysis suggest interactions between ZIKA-NS2A and multiple adherens junction complex (AJ) components. Functionally, ZIKV-NS2A, but not DENV-NS2A, destabilizes the AJ complex, resulting in impaired AJ formation and aberrant radial glial fiber scaffolding in the embryonic mouse cortex. Similarly, ZIKA-NS2A, but not DENV-NS2A, reduces radial glial cell proliferation and causes AJ deficits in human forebrain organoids. Together, our results reveal pathogenic mechanisms underlying ZIKV infection in the developing mammalian brain.
Identifier: FSU_pmch_28826723 (IID), 10.1016/j.stem.2017.07.014 (DOI), PMC5600197 (PMCID), 28826723 (RID), 28826723 (EID), S1934-5909(17)30293-X (PII)
Keywords: Zika virus, Adherens junction, Cortical neurogenesis, Flavivirus, Human organoid, Human protein microarray, Microcephaly, Neural stem cell, Neuronal migration, Radial glial cell
Grant Number: R01 GM111514, P01 NS097206, R35 NS097370, T32 GM007814, R21 MH087874, T32 GM007309, T32 GM007445, R33 MH087874, R37 NS047344, U19 MH106434, R25 NS065729, K12 NS098482, R21 ES021957, R21 NS095348, R21 AI119530, R56 NS047344, R01 NS048271, R01 NS051630, U19 AI131130, R01 MH105128
Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5600197.
Subject(s): Adherens Junctions/metabolism
Animals
Cell Differentiation
Cell Proliferation
Cerebral Cortex/embryology
Cerebral Cortex/metabolism
HEK293 Cells
Humans
Mammals/metabolism
Membrane Proteins/metabolism
Mice
Neurogenesis
Neuroglia/pathology
Protein Binding
Protein Interaction Mapping
Proteolysis
Viral Nonstructural Proteins/metabolism
Zika Virus/metabolism
Zika Virus Infection/pathology
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_pmch_28826723
Owner Institution: FSU
Is Part Of: Cell stem cell.
1875-9777
Issue: iss. 3, vol. 21

Choose the citation style.
Yoon, K. -J., Song, G., Qian, X., Pan, J., Xu, D., Rho, H. -S., … Ming, G. -L. (2017). Zika-Virus-Encoded NS2A Disrupts Mammalian Cortical Neurogenesis by Degrading Adherens Junction Proteins. Cell Stem Cell. Retrieved from http://purl.flvc.org/fsu/fd/FSU_pmch_28826723