Differentiated mosquito adaptive strategies underlie regional dominance of three ECSA sub-lineages in chikungunya virus.

Chikungunya virus (CHIKV) has emerged as a rapidly expanding global health threat and has been reported in 119 countries and territories, with recent outbreaks across Asia, Europe, and the Americas. The East/Central/South African (ECSA) genotype has increasingly predominated in multiple regions, yet the molecular basis of its competitive advantage remains unresolved. Here, we demonstrate that three ECSA sub-lineages-ECSA-IOL, ECSA-2.1, and ECSA-2.2-have independently evolved distinct vector-associated evolutionary patterns that underlie their divergent geographic dominance. Using comparative phylogenomic analyses of complete CHIKV genomes and selection pressure analyses (RELAX/BUSTED/Contrast-FEL), we found that ECSA-2.1 showed intensified selection on structural-protein genes and accumulated substitutions previously associated with Aedes aegypti, explaining its rapid displacement of the Asian genotype across the Americas. In contrast, ECSA-IOL underwent adaptation strategy switching from Aedes albopictus to Ae. aegypti, maintaining its dominance across South and Southeast Asia, while ECSA-2.2 convergently acquired Ae. albopictus adaptation with additional envelope protein mutations, suggesting enhanced adaptive potential. Genome-wide analysis revealed lineage-characteristic and convergent substitutions, providing molecular signatures associated with ECSA competitive advantage. These findings suggest vector niche partitioning as an important driver of CHIKV global expansion dynamics, with potential implications for outbreak forecasting, vector control prioritization, and the design of broadly protective vaccines.