Tracking two decades of global dengue virus lineage dynamics

Abstract Dengue virus (DENV) is genetically diverse, consisting of four antigenically distinct serotypes and extensive sub-serotype variation that can influence epidemiology and control. As DENV continues to expand globally, there is an urgent need to characterize the dynamics of distinct DENV genetic lineages, including their persistence, establishment, and spread. Using a standardized DENV lineage nomenclature system and 37,828 publicly available DENV genomes sampled from 2000–2024, we classified sequences across nine global regions to construct a comprehensive resource of regional lineage distributions over time. We found marked regional differences in lineage diversity, with higher lineage richness in Southeast and East Asia than in the Americas. We further showed that COVID-19-related disruptions were associated with decreased regional lineage persistence and detection of new lineages during 2020–2021, followed by rebounds after 2022 and, in some regions, substantial lineage turnover. Finally, we identified a small set of globally expansive (“cosmopolitan”) lineages that are over-represented in available sequences, including five first-order minor lineages detected in at least seven of nine regions: 3III_B.3, 2II_F.1, 2II_A.1, 1III_A.3, and 1I_K.3. Together, these results demonstrate how standardized lineage classification enables global tracking of emerging DENV diversity and supports targeted genomic surveillance.