ArticlePLoS neglected tropical diseases2025
Genomic hotspots in the DENV-2 serotype (E, NS4B, and NS5 genes) are associated with dengue disease severity in the endemic region of India.
Article in PLoS neglected tropical diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.
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Who cites it
2 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Dengue virus infection and Guillain-Barré syndrome: a systematic review of clinical characteristics, outcomes, and predictors of severity.BMC infectious diseases · 2025Pooled it
- A Case of Intercurrent Dengue and Probable RelapsingPathogens (Basel, Switzerland) · 2025Review
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Authors and funding
18 authors.
Funding
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Abstract
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 yielding 3254 DENV-2 genomes with >50% coverage. However, all of them identified the cosmopolitan genotype of DENV-2, forming a distinct monophyletic cluster in the global phylogenetic tree. Comprehensive variant analysis uncovered 1,618,158 single nucleotide variations (SNVs) across the sequenced DENV-2 population. The clinico-genomic approach carried out in 1294 samples, mild (n = 473), moderate (n = 405) and clinically severe (n = 416), reveals a significant burden of SNVs in various genomic regions linked to differential disease outcomes. Statistical analyses, including Fisher's exact test and phi-correlation, identified hotspot regions in the Envelope (E), NS4B, and NS5 genes, where SNVs were strongly associated with mild and clinically severe phenotypes, providing insights into the genomic determinants of disease severity. Interestingly, the clustering of severity-associated SNVs in these genomic hotspot regions highlights their potential as therapeutic targets within the DENV genome. These findings offer a promising direction for developing early mitigation strategies and targeted interventions to manage the progression of severe DENV infections.
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