Interactions between mosquito genetic background and Wolbachia strain affect dengue virus blocking and fitness in South American populations of Aedes aegypti

The mosquito Aedes aegypti is the primary vector of dengue virus, and the release of mosquitoes infected with the bacterium Wolbachia is an increasingly used strategy to reduce dengue transmission. This approach relies on Wolbachia's ability to suppress virus replication within the mosquito, but the effectiveness of virus suppression and the associated fitness costs may depend on interactions among mosquito genetic background, Wolbachia strain, and dengue virus type. Here, we examined these interactions using mosquito populations from Brazil, Paraguay, and Peru infected with two Wolbachia strains, wMelM and wAlbB, and exposed to dengue virus serotype 1 or serotype 2. We measured dengue virus infection in transmission-relevant tissues and quantified mosquito survival, development, and reproduction under controlled laboratory conditions. Wolbachia infection reduced dengue virus infection overall, but the strength of virus suppression varied among mosquito populations, with the strongest blocking observed in Brazilian mosquitoes and the weakest in Peruvian mosquitoes. Across all populations, the wMelM strain consistently produced stronger dengue virus suppression than wAlbB, whereas mosquitoes infected with wAlbB generally exhibited higher fitness, with fitness effects varying among mosquito populations and life-history traits. Together, these results show that genetic interactions among the mosquito, Wolbachia, and dengue virus shape both virus blocking and mosquito fitness, highlighting trade-offs that may influence the establishment and long-term effectiveness of Wolbachia-based dengue control programs.