Impact of Wolbachia on infection with chikungunya and yellow fever viruses in the mosquito vector Aedes aegypti

Incidence of disease due to dengue (DENV), chikungunya (CHIKV) and yellow fever (YFV) viruses is increasing in many parts of the world. The viruses are primarily transmitted by Aedes aegypti, a highly domesticated mosquito species that is notoriously difficult to control. When transinfected into Ae. aegypti, the intracellular bacterium Wolbachia has recently been shown to inhibit replication of DENVs, CHIKV, malaria parasites and filarial nematodes, providing a potentially powerful biocontrol strategy for human pathogens. Because the extent of pathogen reduction can be influenced by the strain of bacterium, we examined whether the wMel strain of Wolbachia influenced CHIKV and YFV infection in Ae. aegypti. Following exposure to viremic blood meals, CHIKV infection and dissemination rates were significantly reduced in mosquitoes with the wMel strain of Wolbachia compared to Wolbachia-uninfected controls. However, similar rates of infection and dissemination were observed in wMel infected and non-infected Ae. aegypti when intrathoracic inoculation was used to deliver virus. YFV infection, dissemination and replication were similar in wMel-infected and control mosquitoes following intrathoracic inoculations. In contrast, mosquitoes with the wMelPop strain of Wolbachia showed at least a 104 times reduction in YFV RNA copies compared to controls. The extent of reduction in virus infection depended on Wolbachia strain, titer and strain of the virus, and mode of exposure. Although originally proposed for dengue biocontrol, our results indicate a Wolbachia-based strategy also holds considerable promise for YFV and CHIKV suppression.
Author Summary Mosquito-transmitted viruses such as dengue, yellow fever and chikungunya, are responsible for significant morbidity and mortality throughout tropical and sub-tropical regions of the world. These viruses are primarily transmitted by Aedes aegypti, a mosquito that due to its close association with humans has historically been difficult to control. An innovative control strategy involving the release of mosquitoes infected with the intracellular bacterium Wolbachia is currently being developed. This approach is based on the recent discovery that Wolbachia reduces infection of mosquitoes with dengue virus, malaria parasites and filarial nematodes. In the current study, we demonstrated that Wolbachia also blocks infection of chikungunya and yellow fever viruses in Ae. aegypti. The degree of virus inhibition depended on the strain of Wolbachia, the route of virus exposure, the virus strain and the titer of virus that the mosquitoes were exposed to. The implementation of Wolbachia-based control strategies has the capacity to transform the way that mosquitotransmitted diseases are controlled in the future.