4.8 Article

Antigenic evolution of dengue viruses over 20 years

Journal

SCIENCE
Volume 374, Issue 6570, Pages 999-+

Publisher

AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.abk0058

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Infection with dengue viruses leads to protective antibodies, but the viruses can also use heterotypic antibodies to infect immune cells, worsening the disease. The antigenic dynamics of DENV serotypes in Thailand evolved over a 20-year period, with periods of increased similarity between serotypes correlating with changes in epidemic magnitude.
Infection with one of dengue viruses 1 to 4 (DENV1-4) induces protective antibodies against homotypic infection. However, a notable feature of dengue viruses is the ability to use preexisting heterotypic antibodies to infect Fcg receptor-bearing immune cells, leading to higher viral load and immunopathological events that augment disease. We tracked the antigenic dynamics of each DENV serotype by using 1944 sequenced isolates from Bangkok, Thailand, between 1994 and 2014 (348 strains), in comparison with regional and global DENV antigenic diversity (64 strains). Over the course of 20 years, the Thailand DENV serotypes gradually evolved away from one another. However, for brief periods, the serotypes increased in similarity, with corresponding changes in epidemic magnitude. Antigenic evolution within a genotype involved a trade-off between two types of antigenic change (within-serotype and between-serotype), whereas genotype replacement resulted in antigenic change away from all serotypes. These findings provide insights into theorized dynamics in antigenic evolution.

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