Competitive Viral Interference Controls Arbovirus Co-Transmission in Aedes aegypti

Viruses are the primary etiological agents responsible for numerous mosquito-borne diseases, which pose a global threat to humans and their carriers. In this study, we conducted a comprehensive analysis of the simultaneous presence of different viruses in a total of 237 transcriptomic datasets derived from Aedes aegypti (AA), obtained from the SRA and ENA databases to understand its impact on transmission of arboviruses such as Dengue, Zika, and Chikungunya to humans. We investigated the co-occurrence patterns of 21 distinct viruses, encompassing 52 isolates, which are known to be transmitted by mosquitoes. In addition, we used heatmaps, correlation coefficients, estimated count values, and differential gene expression to examine the viral abundance and the significant genes involved in viral co-transmission. We provide novel evidence of a robust antagonistic relationship between the Chikungunya virus and flaviviruses during their co-transmission in AA. Our study confirms that the genes involved in RNAi, ATP-binding, and venom allergen pathways are the pivotal vector interaction hubs in response to viral co-transmission in AA. For the first time, we highlight the critical role of the DDX5 gene in modulating responses to the relative loads of flaviviruses and togaviruses, which could determine the transmission dominance of one over the other.