Shortening of Zika virus CD-loop reduces neurovirulence while preserving antigenicity.
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 co...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2019-03-01
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| Series: | PLoS Neglected Tropical Diseases |
| Online Access: | http://europepmc.org/articles/PMC6424462?pdf=render |
| _version_ | 1818458927466020864 |
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| author | Kenneth H Dinnon Iii Emily N Gallichotte Ethan J Fritch Vineet D Menachery Ralph S Baric |
| author_facet | Kenneth H Dinnon Iii Emily N Gallichotte Ethan J Fritch Vineet D Menachery Ralph S Baric |
| author_sort | Kenneth H Dinnon Iii |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T23:06:14Z |
| format | Article |
| id | doaj.art-94640f83bbc44bb0bdd17fadc2aa608e |
| institution | Directory Open Access Journal |
| issn | 1935-2727 1935-2735 |
| language | English |
| last_indexed | 2024-12-14T23:06:14Z |
| publishDate | 2019-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Neglected Tropical Diseases |
| spelling | doaj.art-94640f83bbc44bb0bdd17fadc2aa608e2022-12-21T22:44:19ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352019-03-01133e000721210.1371/journal.pntd.0007212Shortening of Zika virus CD-loop reduces neurovirulence while preserving antigenicity.Kenneth H Dinnon IiiEmily N GallichotteEthan J FritchVineet D MenacheryRalph S BaricZika 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.http://europepmc.org/articles/PMC6424462?pdf=render |
| spellingShingle | Kenneth H Dinnon Iii Emily N Gallichotte Ethan J Fritch Vineet D Menachery Ralph S Baric Shortening of Zika virus CD-loop reduces neurovirulence while preserving antigenicity. PLoS Neglected Tropical Diseases |
| title | Shortening of Zika virus CD-loop reduces neurovirulence while preserving antigenicity. |
| title_full | Shortening of Zika virus CD-loop reduces neurovirulence while preserving antigenicity. |
| title_fullStr | Shortening of Zika virus CD-loop reduces neurovirulence while preserving antigenicity. |
| title_full_unstemmed | Shortening of Zika virus CD-loop reduces neurovirulence while preserving antigenicity. |
| title_short | Shortening of Zika virus CD-loop reduces neurovirulence while preserving antigenicity. |
| title_sort | shortening of zika virus cd loop reduces neurovirulence while preserving antigenicity |
| url | http://europepmc.org/articles/PMC6424462?pdf=render |
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