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.
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
Publication 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)
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.
Metrics
-
- 1,528
- Page views
-
- 269
- Downloads
-
- 8
- Citations
Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.