Abstract
Wolbachia pipientis from Drosophila melanogaster (wMel) is an endosymbiotic bacterium that restricts transmission of human pathogenic flaviviruses and alphaviruses, including dengue, Zika, and chikungunya viruses, when introduced into the mosquito vector Aedes aegypti. To date, wMel-infected Ae. aegypti have been released in field trials in 5 countries to evaluate the effectiveness of this strategy for disease control. Despite the success in establishing wMel-infected mosquitoes in wild populations, and the well-characterized antiviral capabilities of wMel, transinfecting different or additional Wolbachia strains into Ae. aegypti may improve disease impact, and perhaps more importantly, could provide a strategy to account for the possible evolution of resistant arboviruses. Here, we report the successful transinfection of Ae. aegypti with the Wolbachia strains wMelCS (D. melanogaster), wRi (D. simulans) and wPip (Culex quinquefasciatus) and assess the effects on Ae. aegypti fitness, cytoplasmic incompatibility, tissue tropism and pathogen blocking in a laboratory setting. The results demonstrate that wMelCS provides a similar degree of protection against dengue virus as wMel following an infectious blood meal, and significantly reduces viral RNA levels beyond that of wMel following a direct challenge with infectious virus in mosquitoes, with no additional fitness cost to the host. The protection provided by wRi is markedly weaker than that of wMelCS, consistent with previous characterisations of these lines in Drosophila, while wPip was found to substantially reduce the fitness of Ae. aegypti. Thus, we determine wMelCS as a key candidate for further testing in field-relevant fitness tests and viremic blood feeding challenges in a clinical setting to determine if it may represent an alternative Wolbachia strain with more desirable attributes than wMel for future field testing.
Highlights
Arboviruses transmitted by the Aedes aegypti mosquito, including dengue (DENV), Zika (ZIKV) and chikungunya (CHIKV) are emerging threats that impose an increasing health burden on tropical and subtropical regions of the world
Dengue viruses are transmitted by the Aedes aegypti mosquito, with an estimated 390 million human infections occurring per year worldwide
To predict which Wolbachia strains may provide these traits we looked to past studies, most of which have been performed using natively Wolbachia-infected, artificially transinfected, or introgressed Drosophila lines, with the RNA viruses Drosophila C virus (DCV) or Flock House virus (FHV) as models
Summary
Arboviruses transmitted by the Aedes aegypti mosquito, including dengue (DENV), Zika (ZIKV) and chikungunya (CHIKV) are emerging threats that impose an increasing health burden on tropical and subtropical regions of the world. While these viruses usually cause selflimiting febrile disease, severe manifestations such as hemorrhagic shock can lead to death. It is estimated that at least 40% of all terrestrial arthropod species are infected with Wolbachia [7] which can manipulate host biology to induce feminization, parthenogenesis, cytoplasmic incompatibility (CI) and male-killing [8, 9]. CI, coupled with the maternal transmission (MT) of Wolbachia leads to the rapid invasion of the host population [8, 9]
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