| Literature DB >> 28826723 |
Ki-Jun Yoon1, Guang Song2, Xuyu Qian3, Jianbo Pan4, Dan Xu5, Hee-Sool Rho2, Nam-Shik Kim1, Christa Habela6, Lily Zheng7, Fadi Jacob8, Feiran Zhang9, Emily M Lee10, Wei-Kai Huang11, Francisca Rojas Ringeling12, Caroline Vissers13, Cui Li14, Ling Yuan14, Koeun Kang15, Sunghan Kim15, Junghoon Yeo15, Yichen Cheng10, Sheng Liu4, Zhexing Wen16, Cheng-Feng Qin17, Qingfeng Wu14, Kimberly M Christian18, Hengli Tang10, Peng Jin9, Zhiheng Xu14, Jiang Qian4, Heng Zhu2, Hongjun Song19, Guo-Li Ming20.
Abstract
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.Entities:
Keywords: Zika virus; adherens junction; cortical neurogenesis; flavivirus; human organoid; human protein microarray; microcephaly; neural stem cell; neuronal migration; radial glial cell
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Year: 2017 PMID： 28826723 PMCID： PMC5600197 DOI： 10.1016/j.stem.2017.07.014
Source DB: PubMed Journal: Cell Stem Cell ISSN： 1875-9777 Impact factor: 24.633