Interferon Inducible Guanylate Binding Protein 5 (GBP5) and Its Association With Oxidative Stress Markers in Regulating Dengue Severity: A Clinical and In Vitro Evaluation

Human guanylate-binding proteins (GBPs), induced by interferon in endothelial cells, are being explored as therapeutic targets for viral and metabolic diseases. However, their role in dengue pathogenesis, particularly regarding endothelial leakage in severe cases, remains unclear. To shed some light, the current study assessed mRNA and plasma GBP5 levels in 26 patients with severe dengue (SD), 15 with warning signs (DWW), 15 without warning signs (DWOW), and 10 healthy controls, using RT-PCR and ELISA, respectively. Correlation between plasma GBP5 levels and oxidative stress markers, such as plasma lipid peroxidation, Protein oxidation, and DNA oxidation, was further investigated. GBP5 knockdown was assessed for its effects on oxidative stress and endothelial integrity in the HUVEC model. During the early febrile phase, GBP5 level was significantly elevated in all dengue cases compared to HC; towards the critical phase, there was a sharp decline observed in SD (p < 0.001) and DWW (p < 0.05) cases, which is accompanied by an increased oxidative stress marker, indicating its plausible association with dengue severity. Interferon stimulation of HUVEC cells significantly increased GBP5 expression (p < 0.05) and sustained oxidative stress levels, while GBP5 silencing raised oxidative stress and lowered endothelial integrity. Our findings highlight the potential of GBP5 as a prognostic marker and therapeutic target in the management of dengue.