Antigenic evolution of dengue viruses over multiple decades

Infection with one of the dengue viruses 1-4 (DENV1-4) induces protective antibodies to homotypic infection. However, an exceptional feature of dengue viruses is that they can use preexisting heterotypic antibodies to infect Fcγ receptor-bearing immune cells, leading to higher viral load and immunopathological events that augment disease. We tracked the antigenic dynamics of each DENV serotype using 1,944 sequenced isolates from Bangkok, Thailand between 1994-2014 (n=348) in comparison to regional and global DENV antigenic diversity (n=64 strains). Over the course of 20 years, the Thailand DENV serotypes gradually evolved away from one another. However, for brief periods, the serotypes became more similar, with corresponding changes in epidemic magnitude. Antigenic evolution within a genotype involved a tradeoff in within versus between serotype antigenic change, whereas genotype replacement resulted in antigenic change away from all serotypes. These findings provide insights into theorized dynamics in antigenic evolution.NIAID-NIH Centers of Excellence for Influenza Research and Surveillance contract HHSN272201400008C ERC 80474