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Cell Rep. 2018 Oct 30;25(5):1214-1224. doi: 10.1016/j.celrep.2018.10.006.

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

Author information

1
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA. Electronic address: egallich@email.unc.edu.
2
Department of Epidemiology, University of North Carolina at Chapel Hill School of Public Health, Chapel Hill, NC, USA.
3
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.
4
Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
5
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
6
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA; Department of Epidemiology, University of North Carolina at Chapel Hill School of Public Health, Chapel Hill, NC, USA. Electronic address: rbaric@email.unc.edu.

Abstract

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.

KEYWORDS:

dengue virus; epitope; genotype; neutralizing antibody; vaccine

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