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

ELife
Sidney M BellTrevor Bedford

Abstract

Dengue virus (DENV) exists as four genetically distinct serotypes, each of which is historically assumed to be antigenically uniform. 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 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.

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Citations

Jun 24, 2020·Journal of the Royal Society, Interface·Rahul SubramanianMercedes Pascual
Oct 8, 2020·Tropical Medicine and Infectious Disease·Hernando Gutierrez-BarbosaJoel V Chua
Aug 14, 2020·The Journal of Cell Biology·Fred D MastJohn D Aitchison
May 13, 2021·Nature Communications·Anderson Fernandes BritoNathan D Grubaugh
Nov 19, 2021·Science·Pejman Rohani, John M Drake

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Software Mentioned

IQ
MAFFT
Biopython
Seaborn
SciPy
Matplotlib
TREE
Nextstrain
CVXOPT
Pandas

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