BackgroundVector competence inAedes aegyptiis influenced by various factors. Crucial new control methods can be developed by recognizing which factors affect virus and mosquito interactions.MethodsIn the present study we used three geographically distinctAe. aegyptipopulations and compared their susceptibility to infection by dengue virus serotype 2 (DENV-2). To identify any differences among the three mosquito populations, we evaluated expression levels of immune-related genes and assessed the presence of microbiota that might contribute to the uniqueness in their vector competence.ResultsBased on the results from the DENV-2 competence study, we categorized the three geographically distinctAe. aegyptipopulations into a refractory population (Vilas do Atlântico), a susceptible population (Vero) and a susceptible but low transmission population (California). The immune-related transcripts were highly expressed in the California population but not in the refractory population. However, the Rel-1 gene was upregulated in the Vilas do Atlântico population following ingestion of a non-infectious blood meal, suggesting the gene’s involvement in non-viral responses, such as response to microbiota. Screening of the bacteria, fungi and flaviviruses revealed differences between populations, and any of these could be one of the factors that interfere with the vector competence.ConclusionsThe results reveal potential factors that might impact the virus and mosquito interaction, as well as influence theAe. aegyptirefractory phenotype.Graphical AbstractSupplementary InformationThe online version contains supplementary material available at 10.1186/s13071-023-05784-3.