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Zika-Virus-Encoded NS2A Disrupts Mammalian Cortical Neurogenesis by Degrading Adherens Junction Proteins
Ki-Jun Yoon, Guang Song, Xuyu Qian, Jianbo Pan, Dan Xu, Hee-Sool Rho, Nam-Shik Kim, Christa Habela, Lily Zheng, Fadi Jacob, Feiran Zhang, Emily M. Lee, Wei-Kai Huang, Francisca Rojas Ringeling, Caroline Vissers, Cui Li, Ling Yuan, Koeun Kang, Sunghan Kim, Junghoon Yeo, Yichen Cheng, Sheng Liu, Zhexing Wen, Cheng-Feng Qin, Qingfeng Wu, Kimberly M. Christian, Hengli Tang, Peng Jin, Zhiheng Xu, Jiang Qian, Heng Zhu, Hongjun Song, Guo-li Ming
Cell Stem Cel
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.
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论文编号: |
DOI:10.1016/j.stem.2017.07.014 |
论文题目: |
Zika-Virus-Encoded NS2A Disrupts Mammalian Cortical Neurogenesis by Degrading Adherens Junction Proteins |
英文论文题目: |
Zika-Virus-Encoded NS2A Disrupts Mammalian Cortical Neurogenesis by Degrading Adherens Junction Proteins |
第一作者: |
Ki-Jun Yoon, Guang Song, Xuyu Qian, Jianbo Pan, Dan Xu, Hee-Sool Rho, Nam-Shik Kim, Christa Habela, Lily Zheng, Fadi Jacob, Feiran Zhang, Emily M. Lee, Wei-Kai Huang, Francisca Rojas Ringeling, Caroline Vissers, Cui Li, Ling Yuan, Koeun Kang, Sunghan Kim, Junghoon Yeo, Yichen Cheng, Sheng Liu, Zhexing Wen, Cheng-Feng Qin, Qingfeng Wu, Kimberly M. Christian, Hengli Tang, Peng Jin, Zhiheng Xu, Jiang Qian, Heng Zhu, Hongjun Song, Guo-li Ming |
英文第一作者: |
Ki-Jun Yoon, Guang Song, Xuyu Qian, Jianbo Pan, Dan Xu, Hee-Sool Rho, Nam-Shik Kim, Christa Habela, Lily Zheng, Fadi Jacob, Feiran Zhang, Emily M. Lee, Wei-Kai Huang, Francisca Rojas Ringeling, Caroline Vissers, Cui Li, Ling Yuan, Koeun Kang, Sunghan Kim, Junghoon Yeo, Yichen Cheng, Sheng Liu, Zhexing Wen, Cheng-Feng Qin, Qingfeng Wu, Kimberly M. Christian, Hengli Tang, Peng Jin, Zhiheng Xu, Jiang Qian, Heng Zhu, Hongjun Song, Guo-li Ming |
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2017-09-30 |
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摘要: |
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. |
英文摘要: |
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. |
刊物名称: |
Cell Stem Cel |
英文刊物名称: |
Cell Stem Cel |
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Ki-Jun Yoon, Guang Song, Xuyu Qian, Jianbo Pan, Dan Xu, Hee-Sool Rho, Nam-Shik Kim, Christa Habela, Lily Zheng, Fadi Jacob, Feiran Zhang, Emily M. Lee, Wei-Kai Huang, Francisca Rojas Ringeling, Caroline Vissers, Cui Li, Ling Yuan, Koeun Kang, Sunghan Kim, Junghoon Yeo, Yichen Cheng, Sheng Liu, Zhexing Wen, Cheng-Feng Qin, Qingfeng Wu, Kimberly M. Christian, Hengli Tang, Peng Jin, Zhiheng Xu, Jiang Qian, Heng Zhu, Hongjun Song, Guo-li Ming. Zika-Virus-Encoded NS2A Disrupts Mammalian Cortical Neurogenesis by Degrading Adherens Junction Proteins. Cell Stem Cell. DOI:10.1016/j.stem.2017.07.014 |
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