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Illuminating the in vitro effects of Epstein-Barr virus and vitamin D on immune response in multiple sclerosis patients

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Abstract

Given the complexity of immune complex diseases including multiple sclerosis (MS) and the plausible interactions between different risk factors, delineating the interplay between them would be imperative. The current study aimed to evaluate the in vitro effects of Epstein-Barr virus (EBV) and vitamin D on immune response in MS patients and healthy controls. The status of vitamin D and EBV load was evaluated using multiple techniques. In vitro EBV-infected peripheral blood mononuclear cells (PBMCs), in the presence or absence of vitamin D, were checked for IL-10, IFN-γ, and vitamin D receptor. MS patients showed significantly higher plasma levels of 1,25-(OH)2D but not 25-OHD, increased EBV load, and lower levels of vitamin D receptor (VDR) expression compared with healthy controls. Interestingly, an inverse correlation was observed between VDR expression and EBV load in PBMCs. Indeed, the levels of IFN-γ and IL-10 production were significantly higher in supernatant collected from in vitro EBV–infected PBMCs in MS patients compared with controls. While all vitamin D-treated PBMCs showed reduced levels of IFN-γ production, in vitro treatment of vitamin D showed no influence in IL-10 production. EBV and vitamin D were found to exert opposite in vitro effects on immune dysregulation in these patients. Our results highlight the complex interactions of different risk factors with immune system.

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Abbreviations

1,25-OH2D:

1,25 Di-hydroxy-vitamin D

25-OHD:

25 Hydroxyvitamin D

CNS:

Central nervous system

CYP24A1:

Cytochrome P450 family 24 subfamily A member 1

EDSS:

Expanded Disability Status Scale

EBNA:

Epstein-Barr virus nuclear antigen

EBV:

Epstein–Barr virus

IM:

Infectious mononucleosis

FITC:

Fluorescein isothiocyanate

LMP:

Latent membrane protein

LCL:

Lymphoblastic cell lines

MACS:

Magnetic-activated cell sorting

MS:

Multiple sclerosis

PBMCs:

Peripheral blood mononuclear cells

PP:

Primary progressive

PTLD:

Post-transplant lymphoproliferative disease

PWM:

Pokeweed mitogen

RP:

Relapsing progressive

RR:

Relapsing remitting

SP:

Secondary progressive

VDR:

Vitamin D receptor

VDRE:

Vitamin D responsive elements

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Acknowledgements

We thank all MS patients and healthy individuals for their generous participation in this study.

Funding

This work was supported by Tehran University of Medical Sciences (Grant No.: 95-02-27-31949).

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Authors and Affiliations

  1. Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

    Majid Teymoori-Rad, Talat Mokhtariazad, Ahmad Nejati & Sayed Mahdi Marashi

  2. Multiple Sclerosis Research Centre, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran

    Mohammad Ali Sahraian & Razieh Sadat Kazemi Mozdabadi

  3. Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

    Mohammad Mehdi Amiri & Fazel Shokri

Authors
  1. Majid Teymoori-Rad
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  2. Mohammad Ali Sahraian
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  3. Talat Mokhtariazad
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  4. Ahmad Nejati
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  5. Razieh Sadat Kazemi Mozdabadi
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  6. Mohammad Mehdi Amiri
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  7. Fazel Shokri
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  8. Sayed Mahdi Marashi
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Contributions

Majid Teymoori-Rad, Mohammad Ali Sahraian, Mohammad Mehdi Amiri, Fazel Shokri, and Sayed Mahdi Marashi designed the study and developed the ethical framework for the study. All patients were under the care of Mohammad Ali Sahraian. Material preparation, sample collection, and data analysis were performed by Majid Teymoori-Rad, Razieh Sadat Kazemi Mozdabadi, Ahmad Nejati, Talat Mokhtariazad, Fazel Shokri, and Sayed Mahdi Marashi. The manuscript was written by Majid Teymoori-Rad, Fazel Shokri, and Sayed Mahdi Marashi. All authors read and approved the final manuscript.

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Correspondence to Sayed Mahdi Marashi.

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Teymoori-Rad, M., Sahraian, M.A., Mokhtariazad, T. et al. Illuminating the in vitro effects of Epstein-Barr virus and vitamin D on immune response in multiple sclerosis patients. J. Neurovirol. 27, 260–271 (2021). https://doi.org/10.1007/s13365-021-00951-7

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  • DOI: https://doi.org/10.1007/s13365-021-00951-7

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