Abstract
Background and objectives To investigate the phylogenetic and evolutionary relationships of dengue virus 2 (DENV-2) strains in Sri Lanka and identify probable antigenic B and T cell epitopes in the envelope gene region. Methods Phylogenetic analysis was conducted on the envelope gene region of Sri Lankan DENV-2 strains alongside globally homologous sequences. Selection pressure analysis identified codons under diversifying and purifying selection. Epitope prediction was performed to detect probable antigenic B and T cell epitopes. Results The sequences belonged to two major lineages of the cosmopolitan genotype: major lineage A and F from various geographical regions. Phylogenetic analysis showed segregation into distinct clades, with close sub-clustering of Sri Lankan strains with those from China, Malaysia, Myanmar, Taiwan, and Reunion Island. Selection pressure analysis revealed two sites under diversifying selection, with numerous sites under purifying selection. Epitope prediction detected several linear B and T cell epitopes with probable antigenicity within the envelope gene region. Interpretation and conclusions This study highlights the widespread dominance of the cosmopolitan genotype in Sri Lanka and underscores the role of air travel and human migration in viral transmission and global strain introduction. The presence of diversifying selection at two E gene sites alongside widespread purifying selection suggests evolutionary pressures on viral fitness. The identified B and T cell epitopes represent potential targets for universal vaccine development and therapeutic interventions.