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Dengue virus genotype replacements: investigating viral fitness differences driving the evolution of dengue epidemics
Phylogenetic analyses have revealed that dengue virus (DENV) evolutionary dynamics are often characterized by the replacement of a DENV genotype by another genotype of the same serotype. Such genotype replacements are epidemiologically significant because they can be associated with changes in disease severity and human immunity. However the mechanisms underlying DENV genotype turnover in nature remain poorly defined. In this project, we propose to investigate viral fitness differences driving DENV genotype replacements in two contrasted epidemiologically settings. Cambodia is a dengue hyper-endemic region whereas New Caledonia is a dengue epidemic region. The project will take advantage of recent clinical DENV isolates already available at these two study sites to experimentally evaluate viral fitness differences that could be driving DENV genotype replacements. In addition to DENV phylogenetic characterization, viral fitness will be measured both in wild-type mosquitoes in vivo (vector competence assays) and in mammalian cells in vitro (growth curves).
In short, this project aims to better understand the evolutionary mechanisms driving DENV genotype replacements typically observed during the course of dengue epidemics. Understanding the causes and consequences of genotype replacements has implications for vaccine design because DENV lineages may differ in their antigenic properties.