Transcriptomic Profiling of Diverse Aedes aegypti Strains Reveals Increased Basal-level Immune Activation in Dengue Virus-refractory Populations and Identifies Novel Virus-vector Molecular Interactions

Abstract

Genetic variation among Aedes aegypti populations can greatly influence their vector competence for human pathogens such as the dengue virus (DENV). While intra-species transcriptome differences remain relatively unstudied when compared to coding sequence polymorphisms, they also affect numerous aspects of mosquito biology. Comparative molecular profiling of mosquito strain transcriptomes can therefore provide valuable insight into the regulation of vector competence. We established a panel of A. aegypti strains with varying levels of susceptibility to DENV, comprising both laboratory-maintained strains and field-derived colonies collected from geographically distinct dengue-endemic regions spanning South America, the Caribbean, and Southeast Asia. A comparative genome-wide gene expression microarray-based analysis revealed higher basal levels of numerous immunity-related gene transcripts in DENV-refractory mosquito strains than in susceptible strains, and RNA interference assays further showed different degrees of immune pathway contribution to refractoriness in different strains. By correlating transcript abundance patterns with DENV susceptibility across our panel, we also identified new candidate modulators of DENV infection in the mosquito, and we provide functional evidence for two potential DENV host factors and one potential restriction factor. Our comparative transcriptome dataset thus not only provides valuable information about immune gene regulation and usage in natural refractoriness of mosquito populations to dengue virus but also allows us to identify new molecular interactions between the virus and its mosquito vector.

Antiviral immunity of Anopheles gambiae is highly compartmentalized, with distinct roles for RNA interference and gut microbiota

“…These results suggest that the Toll pathway possesses antiviral activity and that ONNV might possess a mechanism allowing specific Toll pathway inhibition. In A. aegypti, Toll and JAK/STAT are both key anti-DENV immune pathways (15,16,52). In the case of the related alphaviruses SINV (family Togaviridae) and SFV, in Drosophila or A. aegypti, Toll was not involved in antiviral protection (18,48).…”

Dengue virus infection induces chromatin remodeling at locus AAEL006536 in the midgut of Aedes aegypti

“…The dengue virus infection of the cells of the mosquito midgut induces an extensive change on their genome-wide transcriptional profile. [6][7][8] However, the precise molecular mechanisms that lead to a modified transcriptional profile of the midgut cells upon viral infection are not yet fully understood. Identifying the molecules and the mechanisms involved in the transcriptional regulation during a viral infection is essential to fully understand the vector-virus interactions that allow the virus to successfully replicate inside the mosquito cells.…”

Antiviral responses of arthropod vectors: an update on recent advances

“…Recent advances in high throughput technologies, such as transcriptomics and proteomics, for pathogen-host interaction studies [25,52,96,109,117,136], as well as the publication of several vector species genomes including the mosquitoes Culex quinquefasciatus [2], Anopheles gambiae [49] and Aedes aegypti [89] and the tick Ixodes scapularis [46], have led to the discovery of immunity pathway orthologues in these species [65,105]. While there is no midge genome available to date, recent combined efforts of The Pirbright Institute and the European Bioinformatics Institute (part of the European Molecular Biology Laboratory; EBI-EMBL) have led to the first full de novo sequencing project for Culicoides sonorensis.…”