Epstein-Barr Virus miRNAs in Multiple Sclerosis: Unveiling their role in Immune Regulation and Potential for Diagnostic and Therapeutic Innovation

Objective: This study investigates the role of Epstein-Barr virus (EBV)-derived microRNAs (miRNAs) in the pathogenesis of multiple sclerosis (MS), aiming to elucidate their impact on immune-related molecular mechanisms. Methodology: This study was conducted at Ataturk University (Departments of Neurology and Medical Biology), between July 2022 and March 2025, the study included 40 MS patients and 40 healthy controls. Peripheral blood RNA samples were analyzed using Real-Time PCR to measure EBV miRNA and host mRNA expression. Data were evaluated using SPSS v23. Results: EBV-derived miRNA levels were significantly elevated in MS patients. Specifically, BART17-5p, BART10-5p, BHRF1-3 and BART5-3p levels were markedly increased (p<0.001). BART8-5p showed a negative correlation with CREB1 (r=-0.419; p=0.021), suggesting suppression of host signaling pathways. Immune markers such as CXCL3, MALT1, IFNB1, IL6, IL2 and FOXP3 also differed significantly between groups (p=0.005). Moderate correlations were noted between EBV-miRNAs and immune genes (e.g., IFNB1 and BART10-5p: r=0.433; p=0.017). Weak negative correlations were found between BART8-5p and multiple immune-related genes (e.g., IL1B, STAT3, CD4) and between BART19 and IL2 (r=-0.373; p=0.043). Logistic regression revealed that increased BART miRNA levels were associated with elevated MS risk. Conclusion: EBV-derived miRNAs are linked to immune activation and may contribute to MS pathogenesis. These miRNAs may serve as potential biomarkers and therapeutic targets in MS management.