Dengue genetic divergence generates within-serotype antigenic variation, but serotypes dominate evolutionary dynamics
- Fred Hutchinson Cancer Research Center, United States
- University of California, Berkeley, United States
Abstract
Dengue virus (DENV) exists as four genetically distinct serotypes, each of which is historically assumed to be antigenically uniform. However, recent analyses suggest that antigenic heterogeneity may exist within each serotype, but its source, extent and impact remain unclear. Here, we construct a sequence-based model to directly map antigenic change to underlying genetic divergence. We identify 49 specific substitutions and four colinear substitution clusters that robustly predict dengue antigenic relationships. We report moderate antigenic diversity within each serotype, resulting in variation in genotype-specific patterns of heterotypic cross-neutralization. We also quantify the impact of antigenic variation on real-world DENV population dynamics, and find that serotype-level antigenic fitness is a dominant driver of dengue clade turnover. These results provide a more nuanced understanding of the relationship between dengue genetic and antigenic evolution, and quantify the effect of antigenic fitness on dengue evolutionary dynamics.
Data availability
All data, code, model implementations, analyses and figures are available via our online repository at github.com/blab/dengue-antigenic-dynamics
Article and author information
Author details
Funding
National Science Foundation (DGE-1256082)
- Sidney M Bell
Pew Charitable Trusts
- Trevor Bedford
National Institute of General Medical Sciences (R35GM119774-01)
- Trevor Bedford
National Institute of Allergy and Infectious Diseases (R01AI114703-01)
- Leah Katzelnick
National Institute of Allergy and Infectious Diseases (P01AI106695)
- Leah Katzelnick
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Neil M Ferguson, Imperial College London, United Kingdom
Version history
- Received: October 2, 2018
- Accepted: August 5, 2019
- Accepted Manuscript published: August 6, 2019 (version 1)
- Version of Record published: September 6, 2019 (version 2)
- Version of Record updated: April 5, 2023 (version 3)
Copyright
© 2019, Bell et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Dengue genetic divergence generates within-serotype antigenic variation, but serotypes dominate evolutionary dynamics
eLife 8:e42496.
https://doi.org/10.7554/eLife.42496
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