The hsa_circ_0031607 Restricts Dengue Virus Replication in Association with PARP1 and Ferroptosis

Although circular RNAs (circRNAs) are increasingly recognized in antiviral immunity, their roles during DENV infection are largely undefined. Here, we performed transcriptome sequencing of PBMCs from dengue patients stratified by disease phase and severity, identifying differentially expressed circRNAs across severity groups and clinical phases.

Cross-stage intersection identified 15 circRNAs dysregulated across all phases, enriched in ferroptosis, glutathione metabolism, and endocytosis. Among these, hsa_circ_0031607 (circSNX6) was the only one associated with all three pathways and was significantly upregulated in both dengue patients and DENV2-infected HUVECs. circSNX6 overexpression suppressed DENV2 replication, whereas its knockdown enhanced viral propagation. circSNX6 localized to the cytoplasm and physically interacted with PARP1.