Evolutionary history and transmission dynamics of dengue virus type 2 in Africa.

Introduction: Dengue virus serotype 2 (DENV-2) is a major driver of severe dengue outbreaks globally, yet its evolutionary history and transmission dynamics across Africa remain incompletely understood. Methods: To clarify its origins, introduction pathways, and patterns of regional spread, we compiled all available full-length DENV-2 genomes up to 16 July 2025, prioritizing African sequences while retaining representative global references. After quality filtering and down-sampling, a final dataset of 414 genomes was analyzed. Sequences were screened for recombination using RDP4 and analyzed with maximum-likelihood phylogenetics in IQ-TREE with 1,000 ultrafast bootstrap replicates. Temporal dynamics were inferred using time-scaled phylogenies reconstructed in BEAST under a strict molecular clock and exponential-growth coalescent prior, while viral dispersal was examined through discrete-trait phylogeographic analyses with Bayesian stochastic search variable selection. In parallel, single-nucleotide polymorphisms in the prM, E, and NS1 genes were characterized, and significant sites were mapped onto corresponding protein structures. Results and Discussion: Between 1964 and 2024, African DENV-2 diversity was shaped primarily by repeated introductions of the Cosmopolitan genotype, giving rise to geographically structured lineages. Lineage IIB, likely originating from La Réunion in the late 1970s, subsequently disseminated across West, Central, and East Africa, with Burkina Faso emerging as a key regional hub. Lineage IIA, also linked to La Réunion, diverged into two sub-lineages that expanded through East and Central Africa and extended into South Asia. In contrast, lineages IID and IIF were detected only sporadically, with limited geographic representation and no evidence of sustained regional expansion. Despite substantial genetic variation across prM, E, and NS1, relatively few significant non-synonymous mutations were identified, and critical N-glycosylation motifs remained conserved. This pattern suggests that epidemiological connectivity and repeated viral introductions, rather than sustained positive selection at major functional loci, are the dominant forces shaping DENV-2 spread in Africa. Overall, our findings highlight the central role of recurrent introductions and regional transmission networks in structuring DENV-2 circulation across the continent and emphasize the need for strengthened genomic surveillance to track lineage emergence and improve evidence-based dengue prevention and control strategies.