title: Zika Virus Disrupts Neural Progenitor Development and Leads to Microcephaly in Mice.
abstract: The link between Zika virus (ZIKV) infection and microcephaly has raised urgent global alarm. The historical African ZIKV MR766 was recently shown to infect cultured human neural precursor cells (NPCs), but unlike the contemporary ZIKV strains, it is not believed to cause microcephaly. Here we investigated whether the Asian ZIKV strain SZ01 could infect NPCs in vivo and affect brain development. We found that SZ01 replicates efficiently in embryonic mouse brain by directly targeting different neuronal linages. ZIKV infection leads to cell-cycle arrest, apoptosis, and inhibition of NPC differentiation, resulting in cortical thinning and microcephaly. Global gene expression analysis of infected brains reveals upregulation of candidate flavirus entry receptors and dysregulation of genes associated with immune response, apoptosis, and microcephaly. Our model provides evidence for a direct link between Zika virus infection and microcephaly, with potential for further exploration of the underlying mechanisms and management of ZIKV-related pathological effects during brain development.
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Cui
authors.initials: C
authors.lastname: Li
authors.affiliation: Institute of Life Sciences, Fuzhou University, Fuzhou 350116, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Xu
authors.affiliation: Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ye
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Hong
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yisheng
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China; Guangxi Medical University, Nanning 530021, China.
authors.forename: Nana
authors.initials: N
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China. Electronic address: qincf@bmi.ac.cn.
authors.forename: Cheng-Feng
authors.initials: CF
authors.lastname: Qin
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China; Parkinson's Disease Center, Beijing Institute for Brain Disorders, Beijing 100101, China. Electronic address: zhxu@genetics.ac.cn.
authors.forename: Zhiheng
authors.initials: Z
authors.lastname: Xu
mesh_terms: D000818:Animals; D001921:Brain / Q000196:embryology / Q000473:pathology / Q000821:virology; D002453:Cell Cycle / Q000235:genetics; D016923:Cell Death / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D004622:Embryo, Mammalian / Q000276:immunology / Q000473:pathology / Q000821:virology; D005786:Gene Expression Regulation; D007109:Immunity; D008813:Mice, Inbred ICR; D008831:Microcephaly / Q000235:genetics / Q000276:immunology / Q000473:pathology* / Q000821:virology*; D058953:Neural Stem Cells / Q000473:pathology* / Q000821:virology*; D014779:Virus Replication; D000071244:Zika Virus / Q000502:physiology*; D000071243:Zika Virus Infection / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000821:virology