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The Zika Virus Capsid Disrupts Corticogenesis by Suppressing Dicer Activity and miRNA Biogenesis.
Zeng, Jianxiong; Dong, Shupeng; Luo, Zhifei; Xie, Xiaochun; Fu, Bishi; Li, Ping; Liu, Chengrong; Yang, Xing; Chen, Yujie; Wang, Xin; Liu, Zhenshan; Wu, Jing; Yan, Youzhen; Wang, Feng; Chen, Jian-Fu; Zhang, Jian; Long, Gang; Goldman, Steven A; Li, Shitao; Zhao, Zhen; Liang, Qiming.
Afiliação
  • Zeng J; Department of Physiology and Neuroscience, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Dong S; Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Research Center of Translational Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China.
  • Luo Z; Department of Physiology and Neuroscience, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Xie X; Department of Physiology and Neuroscience, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Fu B; Department of Paediatrics, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan, China; State Key Laboratory of Virology, Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, China.
  • Li P; Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, Zhejiang, China.
  • Liu C; Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Yang X; Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Chen Y; Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
  • Wang X; Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Liu Z; Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Wu J; Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Yan Y; Department of Physiology and Neuroscience, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Wang F; Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Research Center of Translational Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China.
  • Chen JF; Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA, USA.
  • Zhang J; Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Long G; Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
  • Goldman SA; Center for Translational Neuromedicine, University of Rochester, Rochester, NY, USA; Department of Neurology, University of Rochester, Rochester, NY, USA; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Li S; Department of Microbiology and Immunology, Tulane University, New Orleans, LA, USA. Electronic address: sli38@tulane.edu.
  • Zhao Z; Department of Physiology and Neuroscience, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. Electronic address: zzhao@usc.edu.
  • Liang Q; Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Research Center of Translational Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China. Electronic address: liangqiming@shs
Cell Stem Cell ; 27(4): 618-632.e9, 2020 10 01.
Article em En | MEDLINE | ID: mdl-32763144
ABSTRACT
Zika virus (ZIKV) causes microcephaly and disrupts neurogenesis. Dicer-mediated miRNA biogenesis is required for embryonic brain development and has been suggested to be disrupted upon ZIKV infection. Here we mapped the ZIKV-host interactome in neural stem cells (NSCs) and found that Dicer is specifically targeted by the capsid from ZIKV, but not other flaviviruses, to facilitate ZIKV infection. We identified a capsid mutant (H41R) that loses this interaction and does not suppress Dicer activity. Consistently, ZIKV-H41R is less virulent and does not inhibit neurogenesis in vitro or corticogenesis in utero. Epidemic ZIKV strains contain capsid mutations that increase Dicer binding affinity and enhance pathogenicity. ZIKV-infected NSCs show global dampening of miRNA production, including key miRNAs linked to neurogenesis, which is not observed after ZIKV-H41R infection. Together these findings show that capsid-dependent suppression of Dicer is a major determinant of ZIKV immune evasion and pathogenesis and may underlie ZIKV-related microcephaly.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: MicroRNAs / Zika virus / Infecção por Zika virus / Microcefalia Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: MicroRNAs / Zika virus / Infecção por Zika virus / Microcefalia Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article