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Basic Characteristics of Mutations
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Mutation Site
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H41R |
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Mutation Site Sentence
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We identified a capsid mutant (H41R) that loses this interaction and does not suppress Dicer activity. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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C |
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Standardized Encoding Gene
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capsid
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Genotype/Subtype
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African |
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Viral Reference
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KU321639
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Functional Impact and Mechanisms
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Disease
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Cell line
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Immune
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- |
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Target Gene
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DICER1
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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- |
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Location
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- |
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Literature Information
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PMID
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32763144
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Title
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The Zika Virus Capsid Disrupts Corticogenesis by Suppressing Dicer Activity and miRNA Biogenesis
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Author
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Zeng J,Dong S,Luo Z,Xie X,Fu B,Li P,Liu C,Yang X,Chen Y,Wang X,Liu Z,Wu J,Yan Y,Wang F,Chen JF,Zhang J,Long G,Goldman SA,Li S,Zhao Z,Liang Q
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Journal
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Cell stem cell
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Journal Info
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2020 Oct 1;27(4):618-632
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Abstract
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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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Sequence Data
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-
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