Final Activity Report Summary - DENGUE VECTORS (Local adaptation and genetic interactions between dengue viruses and their mosquito vectors)
The specific compatibility between the genotypes of pathogens and their vectors has important implications for the incidence and evolution of vector-borne diseases. Earlier genetic studies on the interactions between aedes aegypti mosquitoes and dengue viruses (DENV) had most often used laboratory-tractable systems consisting of selected mosquito lines and a reference viral strain. Hence, the overall objective of this project was to test their validity by characterising the genetic specificity of mosquito-virus interactions in a natural system where both vector and viral populations were genetically diverse.
We firstly measured the specificity of interactions between aedes aegypti and DENV by experimentally challenging several mosquito families which were derived from field-collected individuals with different, contemporaneous wild-type isolates of DENV-1. Most indices of vector competence, i.e. of the ability of an insect to be infected and subsequently transmit a pathogen, were strongly dependent on the specific combination of mosquito families and viral isolates, thus demonstrating significant specificity of genetic compatibility.
We subsequently explored the molecular basis of this specificity by examining polymorphisms in key genes of the aedes aegypti ribonucleic acid interference (RNAi) pathway, which formed a major antiviral defence mechanism in mosquitoes. Variation in one gene (Dicer-2) was associated with isolate-specific infection phenotype, suggesting a possible role of this gene in vector-virus specific compatibility. In addition, we identified several genetic polymorphisms in the viral genomes that could be involved in specific interactions with mosquito vectors.
The evidence for genetic specificity of interactions between DENV and aedes aegypti challenged the general relevance of conclusions from laboratory systems which were formed by a single combination of mosquito and DENV strains. Deciphering the molecular basis of specific compatibility between vector and pathogen strains was crucial for developing innovative vector control strategies which aimed to render wild mosquitoes resistant to all possible pathogen strains and predict the epidemic potential of a given virus when introduced into a novel vector population.
We firstly measured the specificity of interactions between aedes aegypti and DENV by experimentally challenging several mosquito families which were derived from field-collected individuals with different, contemporaneous wild-type isolates of DENV-1. Most indices of vector competence, i.e. of the ability of an insect to be infected and subsequently transmit a pathogen, were strongly dependent on the specific combination of mosquito families and viral isolates, thus demonstrating significant specificity of genetic compatibility.
We subsequently explored the molecular basis of this specificity by examining polymorphisms in key genes of the aedes aegypti ribonucleic acid interference (RNAi) pathway, which formed a major antiviral defence mechanism in mosquitoes. Variation in one gene (Dicer-2) was associated with isolate-specific infection phenotype, suggesting a possible role of this gene in vector-virus specific compatibility. In addition, we identified several genetic polymorphisms in the viral genomes that could be involved in specific interactions with mosquito vectors.
The evidence for genetic specificity of interactions between DENV and aedes aegypti challenged the general relevance of conclusions from laboratory systems which were formed by a single combination of mosquito and DENV strains. Deciphering the molecular basis of specific compatibility between vector and pathogen strains was crucial for developing innovative vector control strategies which aimed to render wild mosquitoes resistant to all possible pathogen strains and predict the epidemic potential of a given virus when introduced into a novel vector population.