Dengue genetic divergence generates within-serotype antigenic variation, but serotypes dominate evolutionary dynamics

Abstract
Data availability
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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

The following previously published data sets were used

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Supplementary Tables S3-S7.

https://cdn.elifesciences.org/articles/42496/DOI: 10.1126/science.aac5017

Article and author information

Author details

Sidney M Bell

Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States

Competing interests
The authors declare that no competing interests exist.
Leah Katzelnick

Division of Infectious Diseases and Vaccinology, University of California, Berkeley, Berkeley, United States

Competing interests
The authors declare that no competing interests exist.
Trevor Bedford

Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States

For correspondence
tbedford@fredhutch.org

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-4039-5794

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.

Copyright

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.