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The identification of up-regulated ebv-miR-BHRF1-2-5p targeting MALT1 and ebv-miR-BHRF1-3 in the circulation of
Y F Wang1, D D He1, H W Liang2
1Department of Neurology, the Second Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, China.
Abstract:
Epstein-Barr virus (EBV) is a well-documented aetiological factor for multiple sclerosis (MS). EBV encodes at least 44 microRNAs (miRNAs) that are readily detectable in the circulation of human. Previous studies have demonstrated that EBV-encoded miRNAs regulate host immune response and may serve as biomarkers for EBV-associated diseases. However, the roles of EBV miRNAs in MS are still unknown. To fill the gap, we conducted a comprehensive profiling of 44 mature EBV miRNAs in 30 relapsing-remitting MS (RRMS) patients at relapse and 30 matched healthy controls. Expression levels of ebv-miR-BHRF1-2-5p and ebv-miR-BHRF1-3 were elevated significantly in the circulation and correlated positively with the expanded disability status scale (EDSS) scores of MS patients. Receiver operating characteristic (ROC) analyses confirmed that the expression of these two miRNAs distinguished MS patients clearly from healthy controls. Luciferase assays revealed that ebv-miR-BHRF1-2-5p may directly target MALT1 (mucosa-associated lymphoid tissue lymphoma transport protein 1), a key regulator of immune homeostasis. In conclusion, we described the expression of EBV miRNAs in MS and preliminarily validated the potential target genes of significantly altered EBV miRNAs. The findings may pave the way for prospective study about the pathogenesis of MS.
Insights
Epstein-Barr virus microRNAs, ebv-miR-BHRF1-2-5p and ebv-miR-BHRF1-3, are elevated in multiple sclerosis (MS) patients and correlate with disability. These viral miRNAs may play a role in MS pathogenesis.
Area of Science:
- Virology
- Neuroimmunology
- Molecular Biology
Background:
- Epstein-Barr virus (EBV) is linked to multiple sclerosis (MS) etiology.
- EBV encodes microRNAs (miRNAs) that modulate host immunity and can be detected in circulation.
- The specific role of EBV-encoded miRNAs in MS pathogenesis remains largely unexplored.
Purpose of the Study:
- To comprehensively profile EBV-encoded miRNAs in individuals with relapsing-remitting MS (RRMS).
- To investigate the association between EBV miRNA expression levels and MS clinical parameters.
- To explore potential molecular mechanisms involving EBV miRNAs in MS.
Main Methods:
- Profiling of 44 mature EBV miRNAs in 30 RRMS patients and 30 healthy controls.
- Quantification of miRNA expression in circulation.
- Correlation analysis with Expanded Disability Status Scale (EDSS) scores.
- Receiver Operating Characteristic (ROC) analysis for diagnostic potential.
- Luciferase assays to validate miRNA-target interactions.
Main Results:
- Elevated expression of ebv-miR-BHRF1-2-5p and ebv-miR-BHRF1-3 was observed in MS patients compared to controls.
- Circulating levels of these two EBV miRNAs positively correlated with EDSS scores.
- ROC analysis demonstrated the ability of these miRNAs to differentiate MS patients from healthy individuals.
- Luciferase assays suggested that ebv-miR-BHRF1-2-5p directly targets MALT1.
Conclusions:
- This study characterizes EBV miRNA expression in MS patients.
- Specific EBV miRNAs, ebv-miR-BHRF1-2-5p and ebv-miR-BHRF1-3, show potential as biomarkers for MS and disease severity.
- Preliminary evidence suggests ebv-miR-BHRF1-2-5p may influence immune homeostasis by targeting MALT1, offering insights into MS pathogenesis.

