Abstract
BACKGROUND: Aedes aegypti is the primary vector of arboviruses worldwide, including dengue, Zika, chikungunya, and yellow fever. It is believed to have originated in Africa and migrated to the Americas during the sixteenth and seventeenth centuries, subsequently spreading to Asia and Oceania between the nineteenth and twentieth centuries. These mosquitoes harbor insect-specific viruses (ISVs), which represent the majority of their core virome. Phasivirus phasiense (PCLV), cell-fusing agent virus (CFAV), and Aedes anphevirus (AeAV) stand out for their global distribution in vectors. Within this framework, this study aims to evaluate whether ISVs can provide insights into the continental dispersal history of Ae. aegypti. METHODS: A total of 96 complete sequences from three ISVs (CFAV, AeAV, and PCLV) were analyzed. These were obtained from wild Ae. aegypti collected across four regions: the Americas (45), Asia (38), Africa (12), and Oceania (1), as well as from laboratory colonies originally derived from wild mosquitoes. Of the 45 sequences from the Americas, 12 were newly assembled for this study from mosquito samples collected in Ibagué, Colombia in 2021 (4 per ISV). To reconstruct the vector's dispersal history and compare evolutionary patterns between viruses with and without evidence of recombination, multiple methodological approaches were used: (1) phylogenetic analyses with BEAST1 to estimate divergence times, (2) statistical tests for recombination (Φ-test), (3) recombination network construction using SplitsTree and RDP, and (4) principal component analysis (PCA) to evaluate population structure. RESULTS: The analysis of three ISVs in global Ae. aegypti populations allowed for the inference of the vector's historical dispersal. The results revealed: (1) genetically structured diversity patterns associated with geography, (2) evidence of recombination in PCLV, but not in AeAV and CFAV, and (3) contrasting temporal estimates suggesting multiple introductions into the Americas between the seventeenth and nineteenth centuries, as well as recent dispersal into Oceania. CONCLUSIONS: ISVs are promising tools for studying the dispersal and evolution of Ae. aegypti, although their viral dynamics can influence their effectiveness as evolutionary markers. CFAV, with recombination evidence, reflects strong connectivity among populations. AeAV, despite lacking recombination but high variability, provides accurate insights into recent dispersal. PCLV, with low diversity and regional recombination, is useful for analyzing local population structures.