Abstract
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.
Highlights
Mosquito-transmitted viruses cause significant human morbidity and mortality throughout the world and impose heavy health and economic burdens on developing countries
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
Summary
Mosquito-transmitted viruses cause significant human morbidity and mortality throughout the world and impose heavy health and economic burdens on developing countries. Dengue, caused by infection with any of the four dengue virus (DENV) serotypes, is currently the leading arboviral disease, with millions of cases of classic dengue fever and tens of thousands of deaths annually due to hemorrhagic disease [1]. Yellow fever virus (YFV) has been implicated in an estimated 200,000 clinical cases and 30,000 human deaths annually in the equatorial regions of Africa and South America [2,3]. Effective vaccines against all four DENV serotypes and CHIKV are still at various stages of development and clinical trial [5,6]. A highly effective vaccine against YFV has been administered for over 50 years, rapid vaccination of susceptible populations either prior to or during an epidemic is financially and logistically challenging, in developing countries [2,3]
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