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Published on: December 1, 2023
Epstein-Barr virus-encoded BART9 and BART15 miRNAs are elevated in exosomes of cerebrospinal fluid from
Mina Mohammadinasr1, Soheila Montazersaheb2, Vahid Hosseini2
1Molecular Medicine Research Center, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
Abstract:
Epstein-Barr virus (EBV) infection is approved as the main environmental trigger of multiple sclerosis (MS). In this path, we quantified ebv-miR-BART9-3p and ebv-miR-BART15 in exosomes of cerebrospinal fluid (CSF) of untreated relapsing-remitting MS (RRMS) patients in comparison with the control group. Interestingly, patients displayed significant upregulation of ebv-miR-BART9-3p (18.4-fold) and ebv-miR-BART15 (3.1-fold) expression in CSF exosomes. Moreover, the expression levels of hsa-miR-21-5p and hsa-miR-146a-5p were found to be significantly elevated in the CSF samples obtained from the patient group compared to those obtained from the HC group. The levels of Interferon-gamma (IFN-γ), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-17 (IL-17), interleukin-23 (IL-23), transforming growth factor beta (TGF-β), and tumor necrosis factor-alpha (TNF-α) were observed to be significantly elevated in the serum and CSF exosomes of the patients. The highest increase was observed in TGF-β (8.5-fold), followed by IL-23 (3.9-fold) in CSF exosomes. These findings are in agreement with the association between EBV infection and inflammatory cytokines induction. Furthermore, the ratios of TGF-β: TNF-α and TGF-β: IFN-γ attained values of 4 to 16.4 and 1.3 to 3.6, respectively, in the CSF exosomes of the patients, in comparison to those of the control group. These findings show EBV activity in RRMS patients is different from that of healthy ones. Elevation of ebv-miR-BART9-3p, ebv-miR-BART15, and inflammatory cytokines expression in CSF exosomes in RRMS patients provides a substantial link between EBV activity and the onset of the disease, as well as the transition from EBV infection to MS.
Insights
Epstein-Barr virus (EBV) infection is linked to multiple sclerosis (MS). This study found elevated EBV microRNAs and inflammatory cytokines in the cerebrospinal fluid of MS patients, suggesting a role in disease development.
Area of Science:
- Neuroimmunology
- Virology
- Molecular Biology
Background:
- Epstein-Barr virus (EBV) is implicated as a key environmental factor in the pathogenesis of multiple sclerosis (MS).
- Exosomes play a role in intercellular communication and can carry viral components and host immune mediators.
Purpose of the Study:
- To investigate the expression of specific EBV-encoded microRNAs (miRNAs) and host inflammatory cytokines within exosomes derived from the cerebrospinal fluid (CSF) of untreated relapsing-remitting MS (RRMS) patients.
- To establish a potential link between EBV activity, exosomal miRNA profiles, and inflammatory markers in the context of MS.
Main Methods:
- Exosomes were isolated from the CSF of untreated RRMS patients and a control group.
- Quantitative analysis was performed to measure the expression levels of EBV-specific miRNAs (ebv-miR-BART9-3p, ebv-miR-BART15) and host miRNAs (hsa-miR-21-5p, hsa-miR-146a-5p) within these exosomes.
- Levels of key inflammatory cytokines (IFN-γ, IL-1β, IL-6, IL-17, IL-23, TGF-β, TNF-α) were quantified in serum and CSF exosomes.
Main Results:
- Significant upregulation of ebv-miR-BART9-3p (18.4-fold) and ebv-miR-BART15 (3.1-fold) was observed in CSF exosomes of RRMS patients compared to controls.
- Host miRNAs hsa-miR-21-5p and hsa-miR-146a-5p were also significantly elevated in RRMS patient CSF exosomes.
- Elevated levels of multiple inflammatory cytokines, notably TGF-β (8.5-fold) and IL-23 (3.9-fold), were detected in CSF exosomes of RRMS patients.
Conclusions:
- The distinct expression patterns of EBV-derived miRNAs and inflammatory cytokines in CSF exosomes differentiate RRMS patients from healthy individuals.
- The observed elevation of ebv-miR-BART9-3p, ebv-miR-BART15, and inflammatory cytokines in CSF exosomes provides strong evidence for a link between EBV activity and MS pathogenesis.
- These findings suggest that exosomal EBV miRNAs and cytokines may contribute to the onset and progression of MS following EBV infection.
