biostudies-literatureRavi VGIISER, South AsiaRockefeller FoundationBill and Melinda Gates FoundationAIDS Healthcare Foundatione0013034https://www.ebi.ac.uk/biostudies/studies/S-EPMC12040166biostudies-literatureUnknown19(4)Dengue virus (DENV) infection manifests a wide spectrum of clinical outcomes, ranging from mild fever to severe and potentially fatal disease, yet the factors driving this variability remain poorly understood. This study aims to unravel the relationship between clinical manifestations of dengue and the genetic diversity of the virus, providing insights into the genomic variability driving disease severity. To achieve this, serum samples were collected during a dengue outbreak in National Capital Region-Delhi, India, from June to November 2023. Serotyping of RNA isolated from 4,045 clinical serum samples revealed DENV-2 as the predominant serotype in circulation (n = 3702). Whole-genome sequencing for 3702 clinical samples was performed using Oxford Nanopore Technology (ONT) further yieldinPLoS neglected tropical diseasesGenomic hotspots in the DENV-2 serotype (E, NS4B, and NS5 genes) are associated with dengue disease severity in the endemic region of India.PMC12040166GAP0276INV-0335782021 HTH 018GAP0248Mohite RKanikaRavi VMishra PSethi TTarai BLiu CSCYadav AChaudhary KPandey RSoni JBudhiraja SImran MShukla RNehaKhare KKhosla PHalder SfalseGenomic hotspots in the DENV-2 serotype (E, NS4B, and NS5 genes) are associated with dengue disease severity in the endemic region of India.Dengue virus (DENV) infection manifests a wide spectrum of clinical outcomes, ranging from mild fever to severe and potentially fatal disease, yet the factors driving this variability remain poorly understood. This study aims to unravel the relationship between clinical manifestations of dengue and the genetic diversity of the virus, providing insights into the genomic variability driving disease severity. To achieve this, serum samples were collected during a dengue outbreak in National Capital Region-Delhi, India, from June to November 2023. Serotyping of RNA isolated from 4,045 clinical serum samples revealed DENV-2 as the predominant serotype in circulation (n = 3702). Whole-genome sequencing for 3702 clinical samples was performed using Oxford Nanopore Technology (ONT) further yieldin2025-01-01T00:00:00Z2025 Apr2026-06-01T10:18:43.801Z2025-07-10T03:09:12.1ZS-EPMC120401664029992510.1371/journal.pntd.0013034