Selection on Aedes aegypti alters Wolbachia-mediated dengue virus blocking and fitness

The dengue, Zika and chikungunya viruses are transmitted by the mosquito Aedes aegypti and pose a substantial threat to global public health. Current vaccines and mosquito control strategies have limited efficacy, so novel interventions are needed^1,2. Wolbachia are bacteria that inhabit insect cells and have been found to reduce viral infection-a phenotype that is referred to as viral 'blocking'³. Although not naturally found in A. aegypti⁴, Wolbachia were stably introduced into this mosquito in 2011^4,5 and were shown to reduce the transmission potential of dengue, Zika and chikungunya^6,7. Subsequent field trials showed Wolbachia's ability to spread through A. aegypti populations and reduce the local incidence of dengue fever⁸. Despite these successes, the evolutionary stability of viral blocking is unknown. Here, we utilized artificial selection to reveal genetic variation in the mosquito that affects Wolbachia-mediated dengue blocking. We found that mosquitoes exhibiting weaker blocking also have reduced fitness, suggesting the potential for natural selection to maintain blocking. We also identified A. aegypti genes that affect blocking strength, shedding light on a possible mechanism for the trait. These results will inform the use of Wolbachia as biocontrol agents against mosquito-borne viruses and direct further research into measuring and improving their efficacy.