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Shortening of Zika virus CD-loop reduces neurovirulence while preserving antigenicity.
- Source :
-
PLoS Neglected Tropical Diseases . 3/7/2019, Vol. 13 Issue 3, p1-14. 14p. - Publication Year :
- 2019
-
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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *ZIKA virus
Subjects
Details
- Language :
- English
- ISSN :
- 19352727
- Volume :
- 13
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- PLoS Neglected Tropical Diseases
- Publication Type :
- Academic Journal
- Accession number :
- 135119876
- Full Text :
- https://doi.org/10.1371/journal.pntd.0007212