Dengue Virus Type 2: Global Epidemiology, Molecular Evolution, and Immune Response Insights

Dengue fever is a globally prevalent arboviral disease caused by four serotypes of dengue virus (DENV), DENV−2 emerges as the most clinically consequential due to its expanding geographic spread and intensifying outbreaks worldwide, while its long-term evolutionary trajectories and genotype-specific transmission features remain insufficiently resolved. Through the integration of global surveillance data from 2014–2024 with complete genome sequences, this study delineates the spatiotemporal spread patterns of DENV−2, reconstructs phylogenetic relationships across its six genotypes, and characterizes key genomic variations, including amino acid substitutions, recombination signals, and divergence between structural and non-structural proteins. Our analysis further reveals a rising trend in global DENV−2 activity, accompanied by recurrent epidemics in Southeast Asia, South America and East Africa and recent autochthonous transmission in temperate Europe with this expansion fueled by climate variability, human mobility and vector adaptation. Phylogenetically, the cosmopolitan genotype dominates globally whereas Asian II and American lineages are geographically constrained, and the Asian/American recombinant lineage persists in parts of Asia and Latin America. Additionally, comparative genomic analyses highlight genotype-dependent mutation heterogeneity and thirteen validated T-cell epitopes enriched in non-structural regions, which underscore relevance to CD8⁺ immunity. The review synthesizes critical insights into DENV−2 evolution, adaptation and immunogenicity, emphasizing the need for strengthened genomic surveillance and prioritization of conserved targets for next-generation dengue vaccines.