Dengue fever is the most important mosquito-borne viral disease of humans with more than 50 million cases estimated annually in more than 100 countries1,2. Disturbingly, the geographic range of dengue is currently expanding and the severity of outbreaks is increasing2,3,4. Control options for dengue are very limited and currently focus on reducing population abundance of the major mosquito vector, Aedes aegypti5,6. These strategies are failing to reduce dengue incidence in tropical communities and there is an urgent need for effective alternatives. It has been proposed that endosymbiotic bacterial Wolbachia infections of insects might be used in novel strategies for dengue control7,8,9. For example, the wMelPop-CLA Wolbachia strain reduces the lifespan of adult A. aegypti mosquitoes in stably transinfected lines8. This life-shortening phenotype was predicted to reduce the potential for dengue transmission. The recent discovery that several Wolbachia infections, including wMelPop-CLA, can also directly influence the susceptibility of insects to infection with a range of insect and human pathogens9,10,11 has markedly changed the potential for Wolbachia infections to control human diseases. Here we describe the successful transinfection of A. aegypti with the avirulent wMel strain of Wolbachia, which induces the reproductive phenotype cytoplasmic incompatibility with minimal apparent fitness costs and high maternal transmission, providing optimal phenotypic effects for invasion. Under semi-field conditions, the wMel strain increased from an initial starting frequency of 0.65 to near fixation within a few generations, invading A. aegypti populations at an accelerated rate relative to trials with the wMelPop-CLA strain. We also show that wMel and wMelPop-CLA strains block transmission of dengue serotype 2 (DENV-2) in A. aegypti, forming the basis of a practical approach to dengue suppression12.
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We are grateful to N. Kenny for technical support and to members of the O’Neill laboratory for critical reading of the manuscript. We thank R. Silcock, M. Janes, S. Long, C. Paton and C. Omodei for their assistance in the semi-field cages and laboratory at James Cook University. We are very grateful for all of our volunteers who helped to blood-feed the mosquitoes in the cages and to P. Young for providing the anti-dengue antibodies. This research was supported by a grant from the Foundation for the National Institutes of Health through the Grand Challenges in Global Health Initiative of the Bill and Melinda Gates Foundation, The National Health and Medical Research Council, Australia, the RAPIDD program of the NIH, the Climate and Health Cluster of the CSIRO Flagship collaboration Fund and fellowships from the Australian Research Council.
The authors declare no competing financial interests.
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Walker, T., Johnson, P., Moreira, L. et al. The wMel Wolbachia strain blocks dengue and invades caged Aedes aegypti populations. Nature 476, 450–453 (2011). https://doi.org/10.1038/nature10355
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