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The wMel Wolbachia strain blocks dengue and invades caged Aedes aegypti populations

Abstract

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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Figure 1: Tissue distribution of the w Mel strain in transinfected A. aegypti female mosquitoes.
Figure 2: Predicted and observed invasion dynamics under semi-field conditions.
Figure 3: Dengue infection levels in mosquitoes.

References

  1. 1

    Calisher, C. H. Persistent emergence of dengue. Emerg. Infect. Dis. 11, 738–739 (2005)

    Article  Google Scholar 

  2. 2

    Kyle, J. L. & Harris, E. Global spread and persistence of dengue. Annu. Rev. Microbiol. 62, 71–92 (2008)

    CAS  Article  Google Scholar 

  3. 3

    Guzman, M. G. et al. Dengue: a continuing global threat. Nature Rev. Microbiol. 8, S7–S16 (2010)

    CAS  Article  Google Scholar 

  4. 4

    Franco, C., Hynes, N. A., Bouri, N. & Henderson, D. A. The dengue threat to the United States. Biosecur. Bioterror. 8, 273–276 (2010)

    Article  Google Scholar 

  5. 5

    Heintze, C., Garrido, M. V. & Kroeger, A. What do community-based dengue control programmes achieve? A systematic review of published evaluations. Trans. R. Soc. Trop. Med. Hyg. 101, 317–325 (2007)

    CAS  Article  Google Scholar 

  6. 6

    Whitehead, S. S., Blaney, J. E., Durbin, A. P. & Murphy, B. R. Prospects for a dengue virus vaccine. Nature Rev. Microbiol. 5, 518–528 (2007)

    CAS  Article  Google Scholar 

  7. 7

    Cook, P. E., McMeniman, C. J. & O’Neill, S. L. Modifying insect population age structure to control vector-borne disease. Adv. Exp. Med. Biol. 627, 126–140 (2008)

    CAS  Article  Google Scholar 

  8. 8

    McMeniman, C. J. et al. Stable introduction of a life-shortening Wolbachia infection into the mosquito Aedes aegypti . Science 323, 141–144 (2009)

    ADS  CAS  Article  Google Scholar 

  9. 9

    Moreira, L. A. et al. A Wolbachia symbiont in Aedes aegypti limits infection with dengue, chikungunya, and Plasmodium . Cell 139, 1268–1278 (2009)

    Article  Google Scholar 

  10. 10

    Hedges, L. M., Brownlie, J. C., O’Neill, S. L. & Johnson, K. N. Wolbachia and virus protection in insects. Science 322, 702 (2008)

    ADS  CAS  Article  Google Scholar 

  11. 11

    Teixeira, L., Ferreira, A. & Ashburner, M. The bacterial symbiont Wolbachia induces resistance to RNA viral infections in Drosophila melanogaster . PLoS Biol. 6, e2 (2008)

    Article  Google Scholar 

  12. 12

    Hoffmann, A. A. et al. Successful establishment of Wolbachia in Aedes populations to suppress dengue transmission. Nature doi:10.1038/nature10356 (this issue).

  13. 13

    Hoffmann, A. A. & Turelli, M. in Influential Passengers: Inherited Microorganisms and Arthropod Reproduction (eds O’Neill, S. L., Hoffmann, A. A. & Werren, J. H. ) 42–80 (Oxford Univ. Press, 1997)

    Google Scholar 

  14. 14

    Turelli, M. & Hoffmann, A. A. Rapid spread of an inherited incompatibility factor in California Drosophila . Nature 353, 440–442 (1991)

    ADS  CAS  Article  Google Scholar 

  15. 15

    Turelli, M. Cytoplasmic incompatibility in populations with overlapping generations. Evolution 64, 232–241 (2010)

    Article  Google Scholar 

  16. 16

    Yeap, H. L. et al. Dynamics of the “popcorn” Wolbachia infection in outbred Aedes aegypti informs prospects for mosquito vector control. Genetics 187, 583–595 (2011)

    CAS  Article  Google Scholar 

  17. 17

    Riegler, M., Sidhu, M., Miller, W. J. & O’Neill, S. L. Evidence for a global Wolbachia replacement in Drosophila melanogaster . Curr. Biol. 15, 1428–1433 (2005)

    CAS  Article  Google Scholar 

  18. 18

    McMeniman, C. J. & O’Neill, S. L. A virulent Wolbachia infection decreases the viability of the dengue vector Aedes aegypti during periods of embryonic quiescence. PLoS Negl. Trop. Dis. 4, e748 (2010)

    Article  Google Scholar 

  19. 19

    Kearney, M., Porter, W. P., Williams, C., Ritchie, S. & Hoffmann, A. A. Integrating biophysical models and evolutionary theory to predict climatic impacts on species’ ranges: the dengue mosquito Aedes aegypti in Australia. Funct. Ecol. 23, 528–538 (2009)

    Article  Google Scholar 

  20. 20

    Montgomery, B. L. & Ritchie, S. A. Roof gutters: a key container for Aedes aegypti and Ochlerotatus notoscriptus (Diptera: Culicidae) in Australia. Am. J. Trop. Med. Hyg. 67, 244–246 (2002)

    Article  Google Scholar 

  21. 21

    Telang, A. & Wells, M. A. The effect of larval and adult nutrition on successful autogenous egg production by a mosquito. J. Insect Physiol. 50, 677–685 (2004)

    CAS  Article  Google Scholar 

  22. 22

    Maciá, A. Differences in performance of Aedes aegypti larvae raised at different densities in tires and ovitraps under field conditions in Argentina. J. Vector Ecol. 31, 371–377 (2006)

    Article  Google Scholar 

  23. 23

    Ritchie, S. A. et al. A secure semi-field system for the study of Aedes aegypti . PLoS Negl. Trop. Dis. 5, e988 (2011)

    Article  Google Scholar 

  24. 24

    Hancock, P. A., Sinkins, S. P. & Godfray, C. J. Population dynamic models of the spread of Wolbachia . Am. Nat. 177, 323–333 (2011)

    Article  Google Scholar 

  25. 25

    Harrington, L. C. et al. Analysis of survival of young and old Aedes aegypti (Diptera: Culicidae) from Puerto Rico and Thailand. J. Med. Entomol. 38, 537–547 (2001)

    CAS  Article  Google Scholar 

  26. 26

    Watts, D. M., Burke, D. S., Harrison, B. A., Whitmire, R. E. & Nisalak, A. Effect of temperature on the vector efficiency of Aedes aegypti for dengue 2 virus. Am. J. Trop. Med. Hyg. 36, 143–152 (1987)

    CAS  Article  Google Scholar 

  27. 27

    Salazar, M. I., Richardson, J. H., Sanchez-Vargas, I., Olson, K. E. & Beaty, B. J. Dengue virus type 2: replication and tropisms in orally infected Aedes aegypti mosquitoes. BMC Microbiol. 7, 9 (2007)

    Article  Google Scholar 

  28. 28

    Bennett, K. E. et al. Variation in vector competence for dengue 2 virus among 24 collections of Aedes aegypti from Mexico and the United States. Am. J. Trop. Med. Hyg. 67, 85–92 (2002)

    Article  Google Scholar 

  29. 29

    Gubler, D. J., Nalim, S., Tan, R., Saipan, H. & Sulianti Saroso, J. Variation in susceptibility to oral infection with dengue viruses among geographic strains of Aedes aegypti . Am. J. Trop. Med. Hyg. 28, 1045–1052 (1979)

    CAS  Article  Google Scholar 

  30. 30

    Bian, G., Xu, Y., Lu, P., Xie, Y. & Xi, Z. The endosymbiotic bacterium Wolbachia induces resistance to dengue virus in Aedes aegypti . PLoS Pathog. 6, e1000833 (2010)

    Article  Google Scholar 

  31. 31

    Glaser, R. L. & Meola, M. A. The native Wolbachia endosymbionts of Drosophila melanogaster and Culex quinquefasciatus increase host resistance to West Nile virus infection. PLoS ONE 5, e11977 (2010)

    ADS  Article  Google Scholar 

  32. 32

    Dobson, S. L., Marsland, E. J., Veneti, Z., Bourtzis, K. & O’Neill, S. L. Characterization of Wolbachia host cell range via the in vitro establishment of infections. Appl. Environ. Microbiol. 68, 656–660 (2002)

    CAS  Article  Google Scholar 

  33. 33

    McMeniman, C. J. et al. Host adaptation of a Wolbachia strain after long-term serial passage in mosquito cell lines. Appl. Environ. Microbiol. 74, 6963–6969 (2008)

    CAS  Article  Google Scholar 

  34. 34

    Wu, M. et al. Phylogenomics of the reproductive parasite Wolbachia pipientis wMel: a streamlined genome overrun by mobile genetic elements. PLoS Biol. 2, e69 (2004)

    Article  Google Scholar 

  35. 35

    Williams, C. R. et al. Rapid estimation of Aedes aegypti population size using simulation modeling, with a novel approach to calibration and field validation. J. Med. Entomol. 45, 1173–1179 (2008)

    Article  Google Scholar 

  36. 36

    Frentiu, F. D., Robinson, J., Young, P. R., McGraw, E. A. & O’Neill, S. L. Wolbachia-mediated resistance to dengue virus infection and death at the cellular level. PLoS ONE 5, e13398 (2010)

    ADS  Article  Google Scholar 

  37. 37

    Richardson, J., Molina-Cruz, A., Salazar, M. I. & Black, W. T. Quantitative analysis of dengue-2 virus RNA during the extrinsic incubation period in individual Aedes aegypti . Am. J. Trop. Med. Hyg. 74, 132–141 (2006)

    CAS  Article  Google Scholar 

Download references

Acknowledgements

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.

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Contributions

T.W. performed transinfection and initial phenotypic characterization of the infection. P.H.J., Y.S.L., Y.D. and S.A.R. performed cage invasion experiments and fecundity assays on outbred mosquito lines. T.W., L.A.M. and F.D.F. carried out vector competence assays. I.I.-O. performed FISH. C.J.M. established cell lines for transinfection. J.A. and P.K. performed cytoplasmic incompatibility and lifespan assays on outbred mosquito lines. A.L.L. undertook modelling studies. T.W. and A.A.H. performed data analysis. T.W., P.H.J., S.L.O. and A.A.H. wrote the paper. S.L.O., A.A.H. and S.A.R. provided oversight of the design and direction of the work.

Corresponding author

Correspondence to S. L. O’Neill.

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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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