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Basic Characteristics of Mutations
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Mutation Site
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346del |
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Mutation Site Sentence
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All mice infected with the Delta346 mutant with detectible virus in their brain (Fig 3B and 3C) maintained the deletion of residue 346, demonstrating that this deletion is stable in vivo (Fig 4A). |
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Mutation Level
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Amino acid level |
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Mutation Type
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Deletion |
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Gene/Protein/Region
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E |
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Standardized Encoding Gene
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envelope
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Genotype/Subtype
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- |
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Viral Reference
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-
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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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Y |
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Target Gene
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-
|
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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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Location
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- |
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Literature Information
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PMID
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30845254
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Title
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Shortening of Zika virus CD-loop reduces neurovirulence while preserving antigenicity
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Author
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Dinnon Iii KH,Gallichotte EN,Fritch EJ,Menachery VD,Baric RS
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Journal
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PLoS neglected tropical diseases
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Journal Info
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2019 Mar 7;13(3):e0007212
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Abstract
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Zika virus (ZIKV) is a mosquito-borne positive sense RNA virus. Recently, ZIKV emerged into the Western hemisphere as a human health threat, with severe disease associated with developmental and neurological complications. The structural envelope protein of ZIKV and other neurotropic flaviviruses contains an extended CD-loop relative to non-neurotropic flaviviruses, and has been shown to augment ZIKV stability and pathogenesis. Here we show that shortening the CD-loop in ZIKV attenuates the virus in mice, by reducing the ability to invade and replicate in the central nervous system. The CD-loop mutation was genetically stable following infection in mice, though secondary site mutations arise adjacent to the CD-loop. Importantly, while shortening of the CD-loop attenuates the virus, the CD-loop mutant maintains antigenicity in immunocompetent mice, eliciting an antibody response that similarly neutralizes both the mutant and wildtype ZIKV. These findings suggest that the extended CD-loop in ZIKV is a determinant of neurotropism and may be a target in live-attenuated vaccine design, for not only ZIKV, but for other neurotropic flaviviruses.
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Sequence Data
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-
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