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Published on: June 13, 2016
Profiling of Epstein-Barr Virus microRNAs in Whole Blood and Exosomes in Multiple Sclerosis
Victoria Hyslop Hvalkof1, Anna Gabriella Stenvig Olsson1, Stefan Gustavsen1
1Danish Multiple Sclerosis Center, Copenhagen University Hospital - Rigshospitalet, Glostrup, Denmark.
Background:
Multiple sclerosis (MS) is a neuroinflammatory, demyelinating disease with Epstein-Barr virus (EBV) suggested as a prerequisite for disease development. EBV expresses 44 microRNAs (miRNAs) with largely unknown functions, but they have been implicated in EBV-infected cell proliferation and immune evasion.
Objectives:
This study investigates EBV miRNAs levels in whole blood and plasma exosomes at baseline and after treatment, and in relation to disease activity based on age-adjusted NfL ratios, in 50 newly diagnosed patients with relapsing-remitting MS (RRMS).
Methods:
EBV miRNAs purified from whole blood and isolated plasma exosomes were measured by qPCR, using TaqMan Array Cards, and correlated to mRNA of GZMA, GZMH, IFN-γ, TNF-α, IL-10, IL-1B, and IL-1R1 in whole blood, measured by qPCR. Serum neurofilament light chain (NfL) and IL-6, plasma anti-EBNA1 antibody titers, occludin, and zonula occludens-1 were measured by various immunoassays.
Results:
The miRNA profiling of whole blood revealed expression of BHRF1 miRNAs in most patients, indicating that EBV is in lytic phase or latency phase III. Higher levels of miR-BART14-3p were observed in patients classified with high disease activity. EBV miRNA levels correlated with anti-EBNA1 antibody titers, biomarkers of inflammation and tight junction proteins.
Insights
Epstein-Barr virus (EBV) microRNAs (miRNAs) were measured in multiple sclerosis (MS) patients. Higher EBV miRNA levels, particularly miR-BART14-3p, correlated with disease activity and inflammation markers.
Area of Science:
- Neuroimmunology
- Virology
Background:
- Multiple sclerosis (MS) is a neuroinflammatory disease potentially linked to Epstein-Barr virus (EBV).
- EBV encodes microRNAs (miRNAs) with roles in cell proliferation and immune evasion, but their function in MS is unclear.
Purpose of the Study:
- To investigate Epstein-Barr virus (EBV) microRNA (miRNA) levels in whole blood and plasma exosomes of newly diagnosed relapsing-remitting MS patients.
- To correlate EBV miRNA levels with disease activity markers, including neurofilament light chain (NfL) ratios, inflammation biomarkers, and tight junction proteins.
Main Methods:
- Quantitative PCR (qPCR) was used to measure EBV miRNAs in whole blood and plasma exosomes.
- Correlations were assessed between EBV miRNA levels and mRNA expression of key inflammatory and immune genes, as well as serum NfL, IL-6, anti-EBNA1 antibody titers, and tight junction proteins.
Main Results:
- EBV miRNAs, including BHRF1 miRNAs, were detected in most MS patients, suggesting EBV lytic or latency phase III.
- Elevated levels of miR-BART14-3p were associated with higher disease activity.
- EBV miRNA levels showed correlations with anti-EBNA1 antibody titers, inflammation biomarkers, and tight junction proteins.
Conclusions:
- EBV miRNAs are detectable in MS patients and may serve as indicators of disease activity.
- The findings suggest a potential role for EBV miRNAs in the pathogenesis of multiple sclerosis.
