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Genetic Variation between Dengue Virus Type 4 Strains Impacts Human Antibody Binding and Neutralization

There are four distinct DENV serotypes, and within DENV4, there are five distinct genotypes. The impact of genotypic diversity is not known, nor is it clear whether infection with one DENV4 genotype results in protective immunity against the other genotypes. To measure the impact of DENV4 genetic di...

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Autores principales: Gallichotte, Emily N., Baric, Thomas J., Nivarthi, Usha, Delacruz, Matthew J., Graham, Rachel, Widman, Douglas G., Yount, Boyd L., Durbin, Anna P., Whitehead, Stephen S., de Silva, Aravinda M., Baric, Ralph S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6226424/
https://www.ncbi.nlm.nih.gov/pubmed/30380413
http://dx.doi.org/10.1016/j.celrep.2018.10.006
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author Gallichotte, Emily N.
Baric, Thomas J.
Nivarthi, Usha
Delacruz, Matthew J.
Graham, Rachel
Widman, Douglas G.
Yount, Boyd L.
Durbin, Anna P.
Whitehead, Stephen S.
de Silva, Aravinda M.
Baric, Ralph S.
author_facet Gallichotte, Emily N.
Baric, Thomas J.
Nivarthi, Usha
Delacruz, Matthew J.
Graham, Rachel
Widman, Douglas G.
Yount, Boyd L.
Durbin, Anna P.
Whitehead, Stephen S.
de Silva, Aravinda M.
Baric, Ralph S.
author_sort Gallichotte, Emily N.
collection PubMed
description There are four distinct DENV serotypes, and within DENV4, there are five distinct genotypes. The impact of genotypic diversity is not known, nor is it clear whether infection with one DENV4 genotype results in protective immunity against the other genotypes. To measure the impact of DENV4 genetic diversity, we generated an isogenic panel of viruses containing the envelope protein from the different genotypes. We characterized many properties of these viruses and find that a small number of amino acids changes within the envelope have disproportionate impacts on virus biology. Additionally, we observe large differences in the ability of DENV4 antibodies, immune sera, and vaccine sera to neutralize the panel, suggesting that DENV4 immunity might not be equally protective against all DENV4s. Our results support the monitoring of changing or emerging DENV genotypes and their role in escaping pre-existing neutralizing antibodies in people who have been vaccinated or exposed to natural DENV4 infections.
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spelling pubmed-62264242018-11-16 Genetic Variation between Dengue Virus Type 4 Strains Impacts Human Antibody Binding and Neutralization Gallichotte, Emily N. Baric, Thomas J. Nivarthi, Usha Delacruz, Matthew J. Graham, Rachel Widman, Douglas G. Yount, Boyd L. Durbin, Anna P. Whitehead, Stephen S. de Silva, Aravinda M. Baric, Ralph S. Cell Rep Article There are four distinct DENV serotypes, and within DENV4, there are five distinct genotypes. The impact of genotypic diversity is not known, nor is it clear whether infection with one DENV4 genotype results in protective immunity against the other genotypes. To measure the impact of DENV4 genetic diversity, we generated an isogenic panel of viruses containing the envelope protein from the different genotypes. We characterized many properties of these viruses and find that a small number of amino acids changes within the envelope have disproportionate impacts on virus biology. Additionally, we observe large differences in the ability of DENV4 antibodies, immune sera, and vaccine sera to neutralize the panel, suggesting that DENV4 immunity might not be equally protective against all DENV4s. Our results support the monitoring of changing or emerging DENV genotypes and their role in escaping pre-existing neutralizing antibodies in people who have been vaccinated or exposed to natural DENV4 infections. Cell Press 2018-10-30 /pmc/articles/PMC6226424/ /pubmed/30380413 http://dx.doi.org/10.1016/j.celrep.2018.10.006 Text en © 2018 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gallichotte, Emily N.
Baric, Thomas J.
Nivarthi, Usha
Delacruz, Matthew J.
Graham, Rachel
Widman, Douglas G.
Yount, Boyd L.
Durbin, Anna P.
Whitehead, Stephen S.
de Silva, Aravinda M.
Baric, Ralph S.
Genetic Variation between Dengue Virus Type 4 Strains Impacts Human Antibody Binding and Neutralization
title Genetic Variation between Dengue Virus Type 4 Strains Impacts Human Antibody Binding and Neutralization
title_full Genetic Variation between Dengue Virus Type 4 Strains Impacts Human Antibody Binding and Neutralization
title_fullStr Genetic Variation between Dengue Virus Type 4 Strains Impacts Human Antibody Binding and Neutralization
title_full_unstemmed Genetic Variation between Dengue Virus Type 4 Strains Impacts Human Antibody Binding and Neutralization
title_short Genetic Variation between Dengue Virus Type 4 Strains Impacts Human Antibody Binding and Neutralization
title_sort genetic variation between dengue virus type 4 strains impacts human antibody binding and neutralization
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6226424/
https://www.ncbi.nlm.nih.gov/pubmed/30380413
http://dx.doi.org/10.1016/j.celrep.2018.10.006
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