Circular RNA Expression Profiles in Crimean-Congo Hemorrhagic Fever: Insights into Disease Pathogenesis and Fatal Outcomes.

Crimean-Congo hemorrhagic fever (CCHF) is a severe tick-borne viral disease with high mortality rates and no approved specific antiviral therapy or vaccine. Circular RNAs (circRNAs) are emerging regulators of gene expression and have been implicated in various infectious and inflammatory diseases; however, their role in CCHF remains unknown. In this study, we investigated circRNA expression profiles in peripheral blood samples from CCHF patients and healthy controls. Total RNA was isolated, enriched for circRNAs using RNase R treatment, and analyzed with the Arraystar Human circRNA Array V2 platform. Differential expression analysis was performed using the limma package in R, followed by RT-PCR validation and bioinformatic analyses. Compared with healthy controls, 15 circRNAs were significantly upregulated and 264 were significantly downregulated in CCHF patients. The most highly upregulated circRNAs included hsa_circ_011083, hsa_circ_092556, hsa_circ_001766, hsa_circ_001569, and hsa_circ_027934, whereas hsa_circ_405788, hsa_circ_104982, hsa_circ_002008, hsa_circ_406768, and hsa_circ_037139 were among the most downregulated. Additionally, 641 and 455 differentially expressed circRNAs were identified in fatal-control and fatal-nonfatal comparisons, respectively. Functional enrichment analyses revealed associations with immune response, inflammatory signaling, and host-virus interaction pathways. To our knowledge, this is the first study to characterize circRNA expression patterns in CCHF, providing novel insights into disease pathogenesis and identifying potential biomarkers associated with disease severity and mortality.