Interferon gamma and inflammatory response genes by weighted gene co-expression network analysis reveal significant associations with severe dengue infection in India

Objective Dengue virus, with four serotypes (DENV 1-4), is transmitted by Aedes aegypti . India carries 34% of global cases, yet studies to understand how the immune system reacts to dengue infection remain limited. Design This study uncovers early transcriptional signatures from whole blood of 112 NS1 positive hospital reported dengue patients and dissect biological processes linked to varying disease severities “with (WS ) and without (-WS ) warning signs”. Results Differential gene expression analysis showed suppressed innate response in WS patients, with downregulated cytokines ( CXCL8, CXCL16, CXCL2, IL1B) and disrupted platelet function. Upregulation was observed in genes related to glycosylation, nervous system, and metabolism. WGCNA module-trait analysis identified interferon response and inflammation as positively correlated with platelet count, highlighting key genes, IFI44L , IFI35 , OAS1 , HERC6 and SAMDL9 contributing to comparative severe outcomes. CTTN involved in maintenance of vascular permeability showed highest significant association with low platelet count. IFI44L emerged as a significant marker, showing highest transcript count difference between patients with platelet counts below 100 × 10ˆ9/L and those between 100-140 × 10ˆ9/L. Conclusion This study advances understanding of dengue infection and identifying probable clinical biomarkers at the initial phase of infection. These findings might hold potential for improving diagnostic and therapeutic strategies.