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

Emily N. Gallichotte, Thomas J. Baric, Usha Nivarthi, Matthew J. Delacruz, Rachel Graham, Douglas G. Widman, Boyd L. Yount, Anna P. Durbin, Stephen S. Whitehead, Aravinda M. de Silva, Ralph S. Baric

Research output: Contribution to journalArticlepeer-review

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. Gallichotte et al. show that subtle genetic variation within the envelope protein across DENV4 genotype viruses can have disproportionally large impacts on many aspects of virus biology. Additionally, genotype viruses are differentially bound and neutralized by DENV antibodies, suggesting that DENV4 immunity may not be equally protective against all DENV4 viruses.

Original languageEnglish (US)
Pages (from-to)1214-1224
Number of pages11
JournalCell Reports
Volume25
Issue number5
DOIs
StatePublished - Oct 30 2018

Keywords

  • dengue virus
  • epitope
  • genotype
  • neutralizing antibody
  • vaccine

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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