TY - JOUR
T1 - Epstein-Barr virus-encoded BART9 and BART15 miRNAs are elevated in exosomes of cerebrospinal fluid from relapsing-remitting multiple sclerosis patients
AU - Mohammadinasr, Mina
AU - Montazersaheb, Soheila
AU - Hosseini, Vahid
AU - Kahroba, Houman
AU - Talebi, Mahnaz
AU - Molavi, Ommoleila
AU - Ayromlou, Hormoz
AU - Hejazi, Mohammad Saeid
N1 - Funding Information:
The authors greatly appreciate Professor Lawrence Steinman's support, constructive input and assistance in editing the manuscript. This is a report of the database from a Ph.D. thesis registered in Tabriz University of Medical Sciences with the Number 62877, financially supported by Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran, [Pazhoohan ID: 70066 and Code: IR.TBZMED.REC.1402.348]. This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Tabriz University of Medical Sciences (IR.TBZMED.REC.1402.348). Informed consent was obtained from all individual participants included in the study. This study was supported by the Molecular Medicine Research Center, Tabriz University of Medical Sciences, (number 70066), Iran. The authors affirm that human research participants provided informed consent for publication.
Funding Information:
The authors greatly appreciate Professor Lawrence Steinman\u2019s support, constructive input, and assistance in editing the manuscript. This is a report of the database from a Ph.D. thesis registered in Tabriz University of Medical Sciences with the Number 62877, financially supported by Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran, [Pazhoohan ID: 70066 and Code: IR.TBZMED.REC.1402.348].
Funding Information:
This study was supported by the Molecular Medicine Research Center, Tabriz University of Medical Sciences , (number 70066), Iran.
Publisher Copyright:
© 2024 Elsevier Ltd
PY - 2024/7/1
Y1 - 2024/7/1
N2 - 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-?), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-17 (IL-17), interleukin-23 (IL-23), transforming growth factor beta (TGF-ß), and tumor necrosis factor-alpha (TNF-a) were observed to be significantly elevated in the serum and CSF exosomes of the patients. The highest increase was observed in TGF-ß (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-ß: TNF-a and TGF-ß: IFN-? 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.
AB - 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-?), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-17 (IL-17), interleukin-23 (IL-23), transforming growth factor beta (TGF-ß), and tumor necrosis factor-alpha (TNF-a) were observed to be significantly elevated in the serum and CSF exosomes of the patients. The highest increase was observed in TGF-ß (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-ß: TNF-a and TGF-ß: IFN-? 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.
KW - Cytokine
KW - Epstein-Barr virus (EBV)
KW - Exosome
KW - miRNAs
KW - Relapsing-remitting multiple sclerosis (RRMS)
U2 - 10.1016/j.cyto.2024.156624
DO - 10.1016/j.cyto.2024.156624
M3 - Article
SN - 1043-4666
VL - 179
JO - Cytokine
JF - Cytokine
M1 - 156624
ER -