Differentiated mosquito adaptive strategies underlie regional dominance of three ECSA sub-lineages in chikungunya virus
- 1State Key Laboratory of Common Mechanism Research for Major Diseases, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Suzhou, Jiangsu, China
Abstract
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. Author summary: Chikungunya virus has spread to 119 countries and territories, with the East/Central/South African (ECSA) genotype now dominating globally. However, the evolutionary mechanisms driving this success have remained unclear. We analyzed over 4,000 viral genomes using comparative phylogenomic and selection-pressure analyses to uncover the hidden drivers of ECSA’s expansion. We discovered that three ECSA sub-lineages have each evolved distinct strategies to adapt to different mosquito species. ECSA-2.1 displaced the Asian genotype in the Americas by intensifying selection on structural-protein genes and fixing Aedes aegypti-adaptive mutations, while ECSA-IOL strategically switched its adaptation from Aedes albopictus to Ae. aegypti to dominate South and Southeast Asia. ECSA-2.2 acquired unique mutations favoring Ae. albopictus and recently emerged in regions where this mosquito is prevalent. Remarkably, vector niche partitioning—not simply faster evolutionary rates—explains why ECSA lineages outcompete other lineages. Our findings establish molecular signatures for tracking variant emergence and identify specific mutations as targets for future functional studies and vaccine development.
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BibTeX
@article{liao2026differentiated,
title = {{Differentiated mosquito adaptive strategies underlie regional dominance of three ECSA sub-lineages in chikungunya virus}},
author = {Yuhua Liao and Jingqi Yang and Jingzhe Shang and Hangyu Zhou and Aiping Wu},
journal = {PLOS Pathogens},
year = {2026},
month = oct,
doi = {10.1371/journal.ppat.1014677},
url = {https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014677},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Differentiated mosquito adaptive strategies underlie regional dominance of three ECSA sub-lineages in chikungunya virus
AU - Yuhua Liao
AU - Jingqi Yang
AU - Jingzhe Shang
AU - Hangyu Zhou
AU - Aiping Wu
PY - 2026
DA - 2026/10/05
JO - PLOS Pathogens
DO - 10.1371/journal.ppat.1014677
UR - https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014677
AB - 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. Author summary: Chikungunya virus has spread to 119 countries and territories, with the East/Central/South African (ECSA) genotype now dominating globally. However, the evolutionary mechanisms driving this success have remained unclear. We analyzed over 4,000 viral genomes using comparative phylogenomic and selection-pressure analyses to uncover the hidden drivers of ECSA’s expansion. We discovered that three ECSA sub-lineages have each evolved distinct strategies to adapt to different mosquito species. ECSA-2.1 displaced the Asian genotype in the Americas by intensifying selection on structural-protein genes and fixing Aedes aegypti-adaptive mutations, while ECSA-IOL strategically switched its adaptation from Aedes albopictus to Ae. aegypti to dominate South and Southeast Asia. ECSA-2.2 acquired unique mutations favoring Ae. albopictus and recently emerged in regions where this mosquito is prevalent. Remarkably, vector niche partitioning—not simply faster evolutionary rates—explains why ECSA lineages outcompete other lineages. Our findings establish molecular signatures for tracking variant emergence and identify specific mutations as targets for future functional studies and vaccine development.
SN - 1553-7374
ER -