Potential role of vector-mediated natural selection in dengue virus genotype/lineage replacements in two epidemiologically contrasted settings
Olivia O’Connor, Tey Putita Ou, Fabien Aubry, Stéphanie Dabo, Sylvie Russet, Dominique Girault, Saraden In, Marine Minier, Sébastian Lequime, Thavry Hoem, Sébastien Boyer, Philippe Dussart, Nicolas Pocquet, Valérie Burtet‐Sarramegna, Louis Lambrechts, Veasna Duong, Myrielle Dupont‐Rouzeyrol
Abstract
Dengue virus (DENV) evolutionary dynamics are characterized by frequent DENV genotype/lineage replacements, potentially associated with changes in disease severity and human immunity. New Caledonia (NC) and Cambodia, two contrasted epidemiological settings, respectively experienced a DENV-1 genotype IV to I replacement in 2012 and a DENV-1 genotype I lineage 3–4 replacement in 2005–2007, both followed by a massive dengue outbreak. However, their underlying evolutionary drivers have not been elucidated. Here, we tested the hypothesis that these genotype/lineage switches reflected a higher transmission fitness of the replacing DENV genotype/lineage in the mosquito vector using in vivo competition experiments. For this purpose, field-derived Aedes aegypti from NC and Cambodia were orally challenged with epidemiologically relevant pairs of four DENV-1 genotype I and IV strains from NC or four DENV-1 genotype I lineage 3 and 4 strains from Cambodia, respectively. The relative transmission fitness of each DENV-1 genotype/lineage was measured by quantitative RT–PCR for infection, dissemination, and transmission rates. Results showed a clear transmission fitness advantage of the replacing DENV-1 genotype I from NC within the vector. A similar but more subtle pattern was observed for the DENV-1 lineage 4 replacement in Cambodia. Our results support the hypothesis that vector-driven selection contributed to the DENV-1 genotype/lineage replacements in these two contrasted epidemiological settings, and reinforce the idea that natural selection taking place within the mosquito vector plays an important role in DENV short-term evolutionary dynamics.