Genetic specificity and potential for local adaptation between dengue viruses and mosquito vectors

Abstract

Background: Several observations support the hypothesis that vector-driven selection plays an important role in shaping dengue virus (DENV) genetic diversity. Clustering of DENV genetic diversity at a particular location may reflect underlying genetic structure of vector populations, which combined with specific vector genotype x virus genotype (G x G) interactions may promote adaptation of viral lineages to local mosquito vector genotypes. Although spatial structure of vector polymorphism at neutral genetic loci is well-documented, existence of G x G interactions between mosquito and virus genotypes has not been formally demonstrated in natural populations. Here we measure G x G interactions in a system representative of a natural situation in Thailand by challenging three isofemale families from field-derived Aedes aegypti with three contemporaneous low-passage isolates of DENV-1.

Results: Among indices of vector competence examined, the proportion of mosquitoes with a midgut infection, viral RNA concentration in the body, and quantity of virus disseminated to the head/legs (but not the proportion of infected mosquitoes with a disseminated infection) strongly depended on the specific combinations of isofemale families and viral isolates, demonstrating significant G x G interactions.

Conclusion: Evidence for genetic specificity of interactions in our simple experimental design indicates that vector competence of Ae. aegypti for DENV is likely governed to a large extent by G x G interactions in genetically diverse, natural populations. This result challenges the general relevance of conclusions from laboratory systems that consist of a single combination of mosquito and DENV genotypes. Combined with earlier evidence for fine-scale genetic structure of natural Ae. aegypti populations, our finding indicates that the necessary conditions for local DENV adaptation to mosquito vectors are met.

Figure 1

Effect of family × isolate interactions on virus infection and dissemination. (a) The proportion of mosquitoes with a midgut infection and (b) proportion of infected mosquitoes with a disseminated infection as a function of mosquito families and virus isolates. In both panels, three isofemale families from a Ratchaburi population (A, B, and C) are ranked on the x-axis according to the mean proportion of infected mosquitoes across isolates. Each line represents a single virus isolate (BKK: Bangkok; KPP: Kamphaeng Phet; RTB: Ratchaburi). Vertical bars show the confidence intervals of the proportions. Crossing lines give an indication of family × isolate interactions.

Figure 2

Effect of family × isolate interactions on viral RNA concentration in mosquito bodies and virus titer in heads/legs. (a) The log-transformed viral RNA copy number per μl of homogenized body (thorax+abdomen) in infected mosquitoes and (b) log-transformed mean number of fluorescent focus units (FFUs) in the head/legs of mosquitoes with a disseminated infection as a function of mosquito families and virus isolates. In both panels, three isofemale families from a Ratchaburi population (A, B, and C) are ranked on the x-axis according to the mean proportion of infected mosquitoes across isolates (consistently with Figure 1). Each line represents a single virus isolate (BKK: Bangkok; KPP: Kamphaeng Phet; RTB: Ratchaburi). Each point represents the mean and vertical bars are the standard errors of the means. Crossing lines give an indication of family × isolate interactions.