Selection upon Wolbachia-mediated dengue virus blocking in Aedes aegypti. Selection upon Wolbachia-mediated dengue virus blocking in Aedes aegypti

The viruses that cause dengue fever, Zika and chikungunya are transmitted by the mosquito, Aedes aegypti and pose great threats to global public health. Current vaccines and treatments against these viruses as well as methods of mosquito control are limited in their efficacy and so novel interventions are needed to reduce disease transmission. Wolbachia are intracellular bacteria that are adapted to spread through insect populations and have been found to reduce viral replication in insects, a phenotype that is referred to as viral ‘blocking’. Although not naturally found in A. aegypti, Wolbachia have been stably introduced into this mosquito via trans-infection over a decade ago and has since been shown to reduce the transmission potential of dengue, Zika and chikungunya. More recently, field trials in the tropics show that Wolbachia can spread through A. aegypti populations and reduce the local incidence of dengue fever. However, it remains unknown how stable this viral blocking phenotype will be in A. aegypti over time. We selected for low and high Wolbachia-mediated dengue blocking alongside a control treatment where mosquitoes were selected at random. Each treatment included 3 independent populations generated randomly from the same ancestral population of mosquitoes using a random number generator. Selection was performed for 4 generations.We reveal significant genetic variation in the A. aegypti genome that is associated with Wolbachia-mediated dengue blocking and responds rapidly to selection. In addition, we find that mosquitoes with weaker Wolbachia-mediated dengue blocking tend to have reduced fitness and appear to be selected against. Together, our data identify candidate genes that can shape Wolbachia-mediated viral blocking and suggest that there is potential for blocking to be maintained by selection. These results will both direct further research into and inform the use of Wolbachia as biocontrol agents against mosquito-borne viruses, including how to measure and improve their efficacy.