|
Basic Characteristics of Mutations
|
|
Mutation Site
|
G150E |
|
Mutation Site Sentence
|
These secondary site mutations, with the exception of G150E, are all structurally located near the CD-loop, suggesting that they may have emerged as a consequence of the shortened CD-loop (Fig 4B and 4C). |
|
Mutation Level
|
Amino acid level |
|
Mutation Type
|
Nonsynonymous substitution |
|
Gene/Protein/Region
|
E |
|
Standardized Encoding Gene
|
envelope
|
|
Genotype/Subtype
|
- |
|
Viral Reference
|
-
|
|
Functional Impact and Mechanisms
|
|
Disease
|
Cell line
|
|
Immune
|
- |
|
Target Gene
|
-
|
|
Clinical and Epidemiological Correlations
|
|
Clinical Information
|
- |
|
Treatment
|
- |
|
Location
|
- |
|
Literature Information
|
|
PMID
|
30845254
|
|
Title
|
Shortening of Zika virus CD-loop reduces neurovirulence while preserving antigenicity
|
|
Author
|
Dinnon Iii KH,Gallichotte EN,Fritch EJ,Menachery VD,Baric RS
|
|
Journal
|
PLoS neglected tropical diseases
|
|
Journal Info
|
2019 Mar 7;13(3):e0007212
|
|
Abstract
|
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.
|
|
Sequence Data
|
-
|