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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Bibliographic Details
Published in:Cell reports (Cambridge) 2018-10, Vol.25 (5), p.1214-1224
Main Authors: 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
Format: Article
Language:English
Subjects:
Animals
Antibodies, Monoclonal - metabolism
Antibodies, Neutralizing - metabolism
Antibodies, Viral - metabolism
Cell Line
Chlorocebus aethiops
Cross Reactions - immunology
Dengue Virus - genetics
Genetic Variation
Genotype
Glycosylation
Humans
Immune Sera - metabolism
Kinetics
Neutralization Tests
Phylogeny
Serogroup
Temperature
Vaccination
Vero Cells
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Summary: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.
ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2018.10.006