Abstract
Genetic strategies that reduce or block pathogen transmission by mosquitoes have been proposed as a means of augmenting current control measures to reduce the growing burden of vector-borne diseases. The endosymbiotic bacterium Wolbachia has long been promoted as a potential vehicle for introducing disease-resistance genes into mosquitoes, thereby making them refractory to the human pathogens they transmit. Given the large overlap in tissue distribution and intracellular localization between Wolbachia and dengue virus in mosquitoes, we conducted experiments to characterize their interactions. Our results show that Wolbachia inhibits viral replication and dissemination in the main dengue vector, Aedes aegypti. Moreover, the virus transmission potential of Wolbachia-infected Ae. aegypti was significantly diminished when compared to wild-type mosquitoes that did not harbor Wolbachia. At 14 days post-infection, Wolbachia completely blocked dengue transmission in at least 37.5% of Ae. aegypti mosquitoes. We also observed that this Wolbachia-mediated viral interference was associated with an elevated basal immunity and increased longevity in the mosquitoes. These results underscore the potential usefulness of Wolbachia-based control strategies for population replacement.
Highlights
Dengue fever and its associated condition, the highly lethal dengue hemorrhagic fever, are emerging globally as the most important arboviral diseases currently threatening human populations
Dengue virus is transmitted to humans by aedine mosquitoes, primarily Aedes aegypti and, to a lesser extent, Aedes albopictus
One novel control strategy for reducing or blocking dengue transmission by mosquitoes involves the endosymbiotic bacterium Wolbachia, which has long been promoted as a potential vehicle for introducing anti-dengue genes into mosquitoes
Summary
Dengue fever and its associated condition, the highly lethal dengue hemorrhagic fever, are emerging globally as the most important arboviral diseases currently threatening human populations. 2.5 billion people are at risk of contracting dengue-associated disease, with an estimated 50–100 million cases occurring each year [1]. Dengue virus (DENV) is transmitted to humans by aedine mosquitoes, primarily Aedes aegypti and, to a lesser extent, Aedes albopictus. No treatment or vaccine is available for dengue fever; vector control is currently the primary intervention tool. One such method is population replacement, in which natural Ae. aegypti populations would be replaced with modified populations that are unable to transmit DENV. Significant progress has been made in producing Ae. aegypti strains that are refractory to DENV [2,3] and in exploring transgene drivers for population replacement [4,5]
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