Field- and clinically derived estimates of Wolbachia-mediated blocking of dengue virus transmission potential in Aedes aegypti mosquitoes

Abstract

The wMel strain of Wolbachia can reduce the permissiveness of Aedes aegypti mosquitoes to disseminated arboviral infections. Here, we report that wMel-infected Ae. aegypti (Ho Chi Minh City background), when directly blood-fed on 141 viremic dengue patients, have lower dengue virus (DENV) transmission potential and have a longer extrinsic incubation period than their wild-type counterparts. The wMel-infected mosquitoes that are field-reared have even greater relative resistance to DENV infection when fed on patient-derived viremic blood meals. This is explained by an increased susceptibility of field-reared wild-type mosquitoes to infection than laboratory-reared counterparts. Collectively, these field- and clinically relevant findings support the continued careful field-testing of wMel introgression for the biocontrol of Ae. aegypti-born arboviruses.

Keywords: Aedes aegypti mosquito; dengue virus; extrinsic incubation period; virus transmission; wMel Wolbachia.

Fig. 1.

Proportion of mosquitoes with infectious virus in their saliva, as a function of log₁₀ plasma viremia (RNA copies per milliliter). Within each panel, the scatterplots and corresponding smooth curves based on logistic regression are shown, with panels separating virus serotypes. Data points represent the proportion of mosquitoes in a given unique cohort of WT or wMel mosquitoes that had infectious saliva on the day of harvesting. Data are pooled from day 10, 12, 14, and 16 harvesting time points. The size of the dot indicates the number of mosquitoes in that cohort.

Fig. 2.

Predicted probability of mosquitoes with DENV-positive saliva for WT and wMel Ae. aegypti mosquitoes, based on a marginal logistic regression model. Each dot point shows the proportion of all mosquitoes that had DENV in their saliva among all mosquitoes that took a blood meal. The corresponding smoothing curves and shading (representing 95% CIs) illustrate the predicted probability of having virus in saliva between days 8 and 20 postexposure to DENV-1 and DENV-4 serotypes (DENV-2 and DENV-3 were excluded due to the small numbers of patients infected with these serotypes).

Fig. 3.

Outcomes of field- and laboratory-rearing vector competence experiments for WT and wMel-infected Aedes aegypti. (A) Proportion of field- and laboratory-reared WT and wMel-infected mosquitoes with infectious saliva after indirect feeding on viremic human blood, as a function of log₁₀ plasma viremia (RNA copies per milliliter). Data are stratified by rearing conditions and the serotype to which the mosquitoes were exposed. Data points represent cohorts of mosquitoes exposed to a single patient blood meal; the size of the dot indicates the mosquito cohort size. (B) wMel-mediated percentage reduction in mosquitoes with infectious saliva, under field- and laboratory-rearing conditions. The boxplot depicts the percentage reductions (medians and interquartile range) in DENV infection rates in saliva, between paired WT/wMel-infected mosquito cohorts (the number of pairs within a group, indicated along the axis). Positive estimates indicate that Wolbachia reduced the relative infection rate; negative estimates indicate a paired cohort had higher infection rates in Wolbachia-infected mosquitoes compared with WT females. Note: DENV-3 is excluded due to small sample sizes.