Cargando…
Relative contribution of nonstructural protein 1 in dengue pathogenesis
Dengue is a major public health concern in the tropical and subtropical world, with no effective treatment. The controversial live attenuated virus vaccine Dengvaxia has boosted the pursuit of subunit vaccine approaches, and nonstructural protein 1 (NS1) has recently emerged as a promising candidate...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478733/ https://www.ncbi.nlm.nih.gov/pubmed/32584412 http://dx.doi.org/10.1084/jem.20191548 |
_version_ | 1783580119350116352 |
---|---|
author | Lee, Pei Xuan Ting, Donald Heng Rong Boey, Clement Peng Hee Tan, Eunice Tze Xin Chia, Janice Zuo Hui Idris, Fakhriedzwan Oo, Yukei Ong, Li Ching Chua, Yen Leong Hapuarachchi, Chanditha Ng, Lee Ching Alonso, Sylvie |
author_facet | Lee, Pei Xuan Ting, Donald Heng Rong Boey, Clement Peng Hee Tan, Eunice Tze Xin Chia, Janice Zuo Hui Idris, Fakhriedzwan Oo, Yukei Ong, Li Ching Chua, Yen Leong Hapuarachchi, Chanditha Ng, Lee Ching Alonso, Sylvie |
author_sort | Lee, Pei Xuan |
collection | PubMed |
description | Dengue is a major public health concern in the tropical and subtropical world, with no effective treatment. The controversial live attenuated virus vaccine Dengvaxia has boosted the pursuit of subunit vaccine approaches, and nonstructural protein 1 (NS1) has recently emerged as a promising candidate. However, we found that NS1 immunization or passive transfer of NS1 antibodies failed to confer protection in symptomatic dengue mouse models using two non–mouse-adapted DENV2 strains that are highly virulent. Exogenous administration of purified NS1 also failed to worsen in vivo vascular leakage in sublethally infected mice. Neither method of NS1 immune neutralization changed the disease outcome of a chimeric strain expressing a vascular leak-potent NS1. Instead, virus chimerization involving the prME structural region indicated that these proteins play a critical role in driving in vivo fitness and virulence of the virus, through induction of key proinflammatory cytokines. This work highlights that the pathogenic role of NS1 is DENV strain dependent, which warrants reevaluation of NS1 as a universal dengue vaccine candidate. |
format | Online Article Text |
id | pubmed-7478733 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-74787332021-03-07 Relative contribution of nonstructural protein 1 in dengue pathogenesis Lee, Pei Xuan Ting, Donald Heng Rong Boey, Clement Peng Hee Tan, Eunice Tze Xin Chia, Janice Zuo Hui Idris, Fakhriedzwan Oo, Yukei Ong, Li Ching Chua, Yen Leong Hapuarachchi, Chanditha Ng, Lee Ching Alonso, Sylvie J Exp Med Article Dengue is a major public health concern in the tropical and subtropical world, with no effective treatment. The controversial live attenuated virus vaccine Dengvaxia has boosted the pursuit of subunit vaccine approaches, and nonstructural protein 1 (NS1) has recently emerged as a promising candidate. However, we found that NS1 immunization or passive transfer of NS1 antibodies failed to confer protection in symptomatic dengue mouse models using two non–mouse-adapted DENV2 strains that are highly virulent. Exogenous administration of purified NS1 also failed to worsen in vivo vascular leakage in sublethally infected mice. Neither method of NS1 immune neutralization changed the disease outcome of a chimeric strain expressing a vascular leak-potent NS1. Instead, virus chimerization involving the prME structural region indicated that these proteins play a critical role in driving in vivo fitness and virulence of the virus, through induction of key proinflammatory cytokines. This work highlights that the pathogenic role of NS1 is DENV strain dependent, which warrants reevaluation of NS1 as a universal dengue vaccine candidate. Rockefeller University Press 2020-06-25 /pmc/articles/PMC7478733/ /pubmed/32584412 http://dx.doi.org/10.1084/jem.20191548 Text en © 2020 Lee et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Article Lee, Pei Xuan Ting, Donald Heng Rong Boey, Clement Peng Hee Tan, Eunice Tze Xin Chia, Janice Zuo Hui Idris, Fakhriedzwan Oo, Yukei Ong, Li Ching Chua, Yen Leong Hapuarachchi, Chanditha Ng, Lee Ching Alonso, Sylvie Relative contribution of nonstructural protein 1 in dengue pathogenesis |
title | Relative contribution of nonstructural protein 1 in dengue pathogenesis |
title_full | Relative contribution of nonstructural protein 1 in dengue pathogenesis |
title_fullStr | Relative contribution of nonstructural protein 1 in dengue pathogenesis |
title_full_unstemmed | Relative contribution of nonstructural protein 1 in dengue pathogenesis |
title_short | Relative contribution of nonstructural protein 1 in dengue pathogenesis |
title_sort | relative contribution of nonstructural protein 1 in dengue pathogenesis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478733/ https://www.ncbi.nlm.nih.gov/pubmed/32584412 http://dx.doi.org/10.1084/jem.20191548 |
work_keys_str_mv | AT leepeixuan relativecontributionofnonstructuralprotein1indenguepathogenesis AT tingdonaldhengrong relativecontributionofnonstructuralprotein1indenguepathogenesis AT boeyclementpenghee relativecontributionofnonstructuralprotein1indenguepathogenesis AT taneunicetzexin relativecontributionofnonstructuralprotein1indenguepathogenesis AT chiajanicezuohui relativecontributionofnonstructuralprotein1indenguepathogenesis AT idrisfakhriedzwan relativecontributionofnonstructuralprotein1indenguepathogenesis AT ooyukei relativecontributionofnonstructuralprotein1indenguepathogenesis AT ongliching relativecontributionofnonstructuralprotein1indenguepathogenesis AT chuayenleong relativecontributionofnonstructuralprotein1indenguepathogenesis AT hapuarachchichanditha relativecontributionofnonstructuralprotein1indenguepathogenesis AT ngleeching relativecontributionofnonstructuralprotein1indenguepathogenesis AT alonsosylvie relativecontributionofnonstructuralprotein1indenguepathogenesis |