Mechanistic insight into complement C3 regulation during chronic HBV infection: effect on viral persistence and host immune response

作者：Baidya A, Dey D, Mallik S, Halder S, Khatun N, Jha R, Nandi S, Chakraborty BC, Dutta A, Banerjee S, Chowdhury A, Ahammed SKM, Datta S · 发表于：Journal of biomedical science · 年份：2026 · DOI：10.1186/s12929-026-01259-6

BACKGROUND: The complement system (CS) is central to antiviral defence, yet many viruses subvert it to escape clearance. Complement-component C3 is the key effector molecule of CS that plays diverse roles in pathogen elimination, inflammation and immune responses, but its regulation during chronic HBV infection (CHI) remains poorly understood. This study examined the mechanisms governing C3 expression in hepatocytes and immune cells during CHI and evaluated the impact of altered C3 levels on viral persistence and host immunity. METHODS: C3 expression was evaluated in blood and liver-tissue samples from patients with CHI and healthy controls using ELISA and RT-PCR. HBV-transfected hepatoma cells were used to examine epigenetic regulation of C3, including promoter methylation, histone deacetylation, and transcription factor phosphorylation. Autophagy-related functions of C3 were assessed by immunofluorescence. Flow cytometry was used to determine the intracellular C3 levels in immune cells of HBV-infected patients and the influence of viral and host factors on C3 expression. Additionally, cytokine production by immune cells and the modulating effect of recombinant C3a on these cytokines was studied. The effect of Tenofovir therapy on C3 concentration was also evaluated. RESULTS: C3 level was found to be significantly diminished in sera and liver-tissues of HBV-infected patients and HBV-expressing hepatoma cells relative to controls. HBX suppressed C3 transcription by restrict...