Abstract
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 needed1,2. 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 20114,5 and were shown to reduce the transmission potential of dengue, Zika and chikungunya6,7. 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.
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Data availability
Raw data are deposited in the Dryad online repository (https://doi.org/10.5061/dryad.6vv10h0) and sequence data are available via the European Nucleotide Archive (accession number: PRJEB33044).
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Acknowledgements
We thank E. Kerton, M. Jones, E. Kennedy, H. Amuzu, G. Terradas, M. Novelo Canto, S. Mole, D. Guy, L. Jimenez, C. Hammer and C. Koh for technical support throughout the experiment. We thank D. Marshall, C. Godfray and K. King for helpful discussions on the manuscript. This work was supported by a grant (APP1103804) from the National Health and Medical Research Council of Australia to E.A.M.
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S.A.F. and E.A.M. conceived and designed the experiments and wrote the manuscript. S.A.F. planned and performed the experiments, including mosquito rearing and infection, selection, RNA and DNA collection and analysis, antibiotic treatment, and life-history measurements. L.T.S. measured candidate gene expression. S.A.F. performed statistical analysis and interpreted the data. S.L.A., A.S., S.F.C. and I.A. collaboratively processed and statistically analysed the genomic data. S.A.F. interpreted the results. J.R.O. and S.A.F. designed the Leslie matrix models to assess mosquito fitness. J.R.O. ran the models. S.A.F. statistically analysed and interpreted the data.
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Supplementary Figs. 1–3, Tables 1–2 and captions for supplementary files.
Supplementary File 1
Realized heritability of Wolbachia-mediated dengue blocking.
Supplementary File 2
A summary of SNPs in genes that are significantly differentiated in the A. aegypti genome between the high and low-blocking populations.
Supplementary File 3
A summary of SNPs in genes that are significantly differentiated in the A. aegypti genome between the random and low-blocking populations.
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Ford, S.A., Allen, S.L., Ohm, J.R. et al. Selection on Aedes aegypti alters Wolbachia-mediated dengue virus blocking and fitness. Nat Microbiol 4, 1832–1839 (2019). https://doi.org/10.1038/s41564-019-0533-3
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DOI: https://doi.org/10.1038/s41564-019-0533-3
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