The Influence of Epstein-Barr virus infection on developing multiple sclerosis
DOI:
https://doi.org/10.12775/JEHS.2023.22.01.004Keywords
Demyelinating Disease, Autoimmune Disease, Infectious disease, Herpes viruses, Infectious Mononucleosis, Viral infectionAbstract
Multiple sclerosis (MS) is the most common inflammatory-demyelinating disease. MS leads to the multifocal damage of the central nervous system, which causes the gradual deterioration of sensory, motor and cognitive functions. The etiology of this disease is not fully understood, but genetic and environmental factors (including the EBV infection) are suspected. In this review, we would like to summarize the state of knowledge over the effect of Epstein-Barr virus infection on developing multiple sclerosis.
Infectious mononucleosis (IM) which is caused by EBV and MS have similar epidemiology: both diseases mainly affect people at a young age, geographical prevalence is also identical. There are many theories that explain the mechanism of the EBV involvement in the development of MS including: the migration of EBV-infected B cells into the Central Nervous System, the theory of molecular mimicry, the induction of αB-crystallin by EBV in lymphoid cells or cooperation of the EBV and other viruses in the development of MS. Observations by physicians from around the world suggest that EBV infection is a strong factor in the development of multiple sclerosis. Epstein-Barr virus is prevalent in the population. There are a lot of evidences that suggest its involvement in the development of multiple sclerosis. Prevention of EBV infection could potentially reduce the amount of cases of MS. However, more researches are needed to clearly confirm the involvement of EBV in the etiopathogenesis of developing MS.
References
Reich DS, Lucchinetti CF, Calabresi PA. Multiple Sclerosis. N Engl J Med. 2018; 378(2):169-180. doi: 10.1056/NEJMra1401483.
Tarlinton RE, Khaibullin T, Granatov E, Martynova E, Rizvanov A, Khaiboullina S. The Interaction between Viral and Environmental Risk Factors in the Pathogenesis of Multiple Sclerosis. Int J Mol Sci. 2019; 20(2):303. doi: 10.3390/ijms20020303.
Horowitz AL, Kaplan RD, Grewe G, White RT, Salberg LM. The ovoid lesion: a new MR observation in patients with multiple sclerosis. AJNR Am J Neuroradiol. 1989;10(2):303-305.
Lucchinetti C, Brück W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H. Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol. 2000; 47(6):707-717. doi: 10.1002/1531-8249(200006)47:6<707::aid-ana3>3.0.co;2-q.
Compston A, Coles A. Multiple sclerosis. Lancet. 2008; 372(9648):1502-1517. doi: 10.1016/S0140-6736(08)61620-7.
Hamad AA, Thivagar ML, Alazzam MB, Alassery F, Hajjej F, Shihab AA. Applying Dynamic Systems to Social Media by Using Controlling Stability, Computational Intelligence and Neuroscience, 2022: 7 (Article ID 4569879) doi.org/10.1155/2022/4569879
Lublin FD, Reingold SC. Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology. 1996;46(4):907-911. doi: 10.1212/wnl.46.4.907.
Trapp BD, Nave KA. Multiple sclerosis: an immune or neurodegenerative disorder? Annu Rev Neurosci. 2008;31: 247-269. doi: 10.1146/annurev.neuro.30.051606.094313.
Ascherio A. Environmental factors in multiple sclerosis. Expert Rev Neurother. 2013;13(12 Suppl):3-9. doi: 10.1586/14737175.2013.865866.
Lucas RM, Hughes AM, Lay ML, Ponsonby AL, Dwyer DE, Taylor BV, Pender MP. Epstein-Barr virus and multiple sclerosis. J Neurol Neurosurg Psychiatry. 2011; 82(10):1142-1148. doi: 10.1136/jnnp-2011-300174.
Lawson-Thorley DA, “Epstein-Barr virus: exploring the immune system,” Nature Reviews Immunology, 2001; 1: 75-82
Donati D. Viral infections and multiple sclerosis. Drug Discov Today Dis Models. 2020; 32:27-33. doi: 10.1016/j.ddmod.2020.02.003.
Lossius A, Riise T, Pugliatti M, Bjørnevik K, Casetta I, Drulovic J, Granieri E, Kampman MT, Landtblom AM, Lauer K, Magalhaes S, Myhr KM, Pekmezovic T, Wesnes K, Wolfson C, Holmøy T. Season of infectious mononucleosis and risk of multiple sclerosis at different latitudes; the EnvIMS Study. Mult Scler. 2014; 20(6):669-674. doi: 10.1177/1352458513505693.
Bjornevik K, Cortese M, Healy BC, Kuhle J, Mina MJ, Leng Y, Elledge SJ, Niebuhr DW, Scher AI, Munger KL, Ascherio A. Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis. Science. 2022; 375(6578):296-301. doi: 10.1126/science.abj8222.
Giovannoni G. Epstein-Barr Virus and MS. Int MS J. 2011; 17(2):44-49.
Gontkiewicz Ł, Biesiada G, Czepiel J, Garlicki A: Przedstawienie przypadków zapalenia wątroby wywołanego wirusem EBV, Forum Medycyny Rodzinnej, 2017; 11(3):136-141
Levin LI, Munger KL, O'Reilly EJ, Falk KI, Ascherio A. Primary infection with the Epstein-Barr virus and risk of multiple sclerosis. Ann Neurol. 2010; 67(6):824-830. doi: 10.1002/ana.21978.
Serafini B, Rosicarelli B, Franciotta D, Magliozzi R, Reynolds R, Cinque P, Andreoni L, Trivedi P, Salvetti M, Faggioni A, Aloisi F. Dysregulated Epstein-Barr virus infection in the multiple sclerosis brain. J Exp Med. 2007; 204(12):2899-2912. doi: 10.1084/jem.20071030
Houen G, Trier NH, Frederiksen JL. Epstein-Barr Virus and Multiple Sclerosis. Front Immunol. 2020; 11:587078. doi: 10.3389/fimmu.2020.587078.
Bar-Or A, Pender MP, Khanna R, Steinman L, Hartung HP, Maniar T, Croze E, Aftab BT, Giovannoni G, Joshi MA. Epstein-Barr Virus in Multiple Sclerosis: Theory and Emerging Immunotherapies. Trends Mol Med. 2020; 26(3):296-310. doi: 10.1016/j.molmed.2019.11.003. Erratum in: Trends Mol Med. 2021; 27(4):410-411.
Harley JB, Chen X, Pujato M, Miller D, Maddox A, Forney C, Magnusen AF, Lynch A, Chetal K, Yukawa M, Barski A, Salomonis N, Kaufman KM, Kottyan LC, Weirauch MT. Transcription factors operate across disease loci, with EBNA2 implicated in autoimmunity. Nat Genet. 2018; 50(5):699-707. doi: 10.1038/s41588-018-0102-3.
Tzartos JS, Khan G, Vossenkamper A, Cruz-Sadaba M, Lonardi S, Sefia E, Meager A, Elia A, Middeldorp JM, Clemens M, Farrell PJ, Giovannoni G, Meier UC. Association of innate immune activation with latent Epstein-Barr virus in active MS lesions. Neurology. 2012; 78(1):15-23. doi: 10.1212/WNL.0b013e31823ed057.
Lünemann JD, Jelcić I, Roberts S, Lutterotti A, Tackenberg B, Martin R, Münz C. EBNA1-specific T cells from patients with multiple sclerosis cross react with myelin antigens and co-produce IFN-gamma and IL-2. J Exp Med. 2008; 205(8):1763-1773. doi: 10.1084/jem.20072397
van Noort JM, Bajramovic JJ, Plomp AC, van Stipdonk MJ. Mistaken self, a novel model that links microbial infections with myelin-directed autoimmunity in multiple sclerosis. J Neuroimmunol. 2000; 105(1):46-57. doi: 10.1016/s0165-5728(00)00181-8.
Fierz W. Multiple sclerosis: an example of pathogenic viral interaction? Virol J. 2017; 14(1):42. doi: 10.1186/s12985-017-0719-3. PMID: 28241767
Pender MP, Csurhes PA, Smith C, Douglas NL, Neller MA, Matthews KK, Beagley L, Rehan S, Crooks P, Hopkins TJ, Blum S, Green KA, Ioannides ZA, Swayne A, Aftab BT, Hooper KD, Burrows SR, Thompson KM, Coulthard A, Khanna R. Epstein-Barr virus-specific T cell therapy for progressive multiple sclerosis. JCI Insight. 2018; 3(22):e124714. doi: 10.1172/jci.insight.124714. Erratum in: JCI Insight. 2020; 5(20)
Jelcic I, Al Nimer F, Wang J, Lentsch V, Planas R, Jelcic I, Madjovski A, Ruhrmann S, Faigle W, Frauenknecht K, Pinilla C, Santos R, Hammer C, Ortiz Y, Opitz L, Grönlund H, Rogler G, Boyman O, Reynolds R, Lutterotti A, Khademi M, Olsson T, Piehl F, Sospedra M, Martin R. Memory B Cells Activate Brain-Homing, Autoreactive CD4+ T Cells in Multiple Sclerosis. Cell. 2018; 175(1):85-100.e23. doi: 10.1016/j.cell.2018.08.011.
Winter S, Martin E, Boutboul D, Lenoir C, Boudjemaa S, Petit A, Picard C, Fischer A, Leverger G, Latour S. Loss of RASGRP1 in humans impairs T-cell expansion leading to Epstein-Barr virus susceptibility. EMBO Mol Med. 2018; 10(2):188-199. doi: 10.15252/emmm.201708292.
Steinman L. The discovery of natalizumab, a potent therapeutic for multiple sclerosis. J Cell Biol. 2012; 199(3):413-416. doi: 10.1083/jcb.201207175.
Olsson T, Barcellos LF, Alfredsson L. Interactions between genetic, lifestyle and environmental risk factors for multiple sclerosis. Nat Rev Neurol. 2017; 13(1):25-36. doi: 10.1038/nrneurol.2016.187.
Mentis AA, Dardiotis E, Grigoriadis N, Petinaki E, Hadjigeorgiou GM. Viruses and Multiple Sclerosis: From Mechanisms and Pathways to Translational Research Opportunities. Mol Neurobiol. 2017; 54(5):3911-3923. doi: 10.1007/s12035-017-0530-6.
Langer-Gould A, Wu J, Lucas R, Smith J, Gonzales E, Amezcua L, Haraszti S, Chen LH, Quach H, James JA, Barcellos LF, Xiang AH. Epstein-Barr virus, cytomegalovirus, and multiple sclerosis susceptibility: A multiethnic study. Neurology. 2017; 89(13):1330-1337. doi: 10.1212/WNL.0000000000004412.
Farrell PJ. Epstein-Barr Virus and Cancer. Annu Rev Pathol. 2019; 14:29-53. doi: 10.1146/annurev-pathmechdis-012418-013023.
Cotsapas C, Mitrovic M, Hafler D. Multiple sclerosis. Handb Clin Neurol. 2018;148:723-730. doi: 10.1016/B978-0-444-64076-5.00046-6.
Wingerchuk DM. Environmental factors in multiple sclerosis: Epstein-Barr virus, vitamin D, and cigarette smoking. Mt Sinai J Med. 2011; 78(2):221-230. doi: 10.1002/msj.20240.
Patsopoulos NA, Barcellos LF, Hintzen RQ, Schaefer C, van Duijn CM, Noble JA, Raj T; IMSGC; ANZgene; Gourraud PA, Stranger BE, Oksenberg J, Olsson T, Taylor BV, Sawcer S, Hafler DA, Carrington M, De Jager PL, de Bakker PI. Fine-mapping the genetic association of the major histocompatibility complex in multiple sclerosis: HLA and non-HLA effects. PLoS Genet. 2013; 9(11):e1003926. doi: 10.1371/journal.pgen.1003926.
Travers BS, Tsang BK, Barton JL. Multiple sclerosis: Diagnosis, disease-modifying therapy and prognosis. Aust J Gen Pract. 2022; 51(4):199-206. doi: 10.31128/AJGP-07-21-6103.
Wildner P, Stasiołek M, Matysiak M. Differential diagnosis of multiple sclerosis and other inflammatory CNS diseases. Mult Scler Relat Disord. 2020; 37:101452. doi: 10.1016/j.msard.2019.101452.
Hauser SL, Cree BAC. Treatment of Multiple Sclerosis: A Review. Am J Med. 2020; 133(12):1380-1390.e2. doi: 10.1016/j.amjmed.2020.05.049.
Walz L, Brooks JC, Shavelle RM, Robertson N, Harding KE. Life expectancy in multiple sclerosis by EDSS score. Mult Scler Relat Disord. 2022; 68:104219. doi: 10.1016/j.msard.2022.104219.
Soelberg Sorensen P, Giovannoni G, Montalban X, Thalheim C, Zaratin P, Comi G. The Multiple Sclerosis Care Unit. Mult Scler. 2019; 25(5):627-636. doi: 10.1177/1352458518807082.
Epstein MA, Achong BG, Barr YM. Virus particles in cultured lymphoblasts from Burkitt’s lymphoma. Lancet. 1964; 1(7335):702-3. doi: 10.1016/s0140-6736(64)91524-7.
Liu F, Zhou ZH. Comparative virion structures of human herpesviruses. In: Arvin A, Campadelli-Fiume G, Mocarski E, Moore PS, Roizman B, Whitley R, Yamanishi K, editors. Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis. Cambridge: Cambridge University Press; 2007. Chapter 3.
Houen G, Trier NH. Epstein-Barr Virus and Systemic Autoimmune Diseases. Front Immunol. 2021; 11:587380. doi: 10.3389/fimmu.2020.587380.
Middleton T, Sugden B. Retention of plasmid DNA in mammalian cells is enhanced by binding of the Epstein-Barr virus replication protein EBNA1. J Virol. 1994; 68(6):4067-71. doi: 10.1128/JVI.68.6.4067-4071.1994.
Wensing B, Farrell PJ. Regulation of cell growth and death by Epstein-Barr virus. Microbes Infect. 2000; 2(1):77-84. doi: 10.1016/s1286-4579(00)00282-3.
Murray PG, Young LS. The Role of the Epstein-Barr virus in human disease. Front Biosci. 2002; 7:d519-40. doi: 10.2741/murray.
Mohseni M, Boniface MP, Graham C. Mononucleosis. 2022. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022.
Abreu A, Nunes S, Botelho C. Eosinophilia in Amoxicillin-Induced Rash in Infectious Mononucleosis. Cureus. 2023; 15(1):e33504. doi: 10.7759/cureus.33504.
Żuk-Wasek A, Charakterystyka białek wirusa Epstein-Barr- ich udział w zakażeniu latentnym i powiązanie z procesami nowotworzenia; 2012:3
Vogler K, Schmidt LS. [Clinical manifestations of Epstein-Barr virus infection in children and adolescents]. Ugeskr Laeger. 2018; 180(20):V09170644. Danish.
Dunmire SK, Verghese PS, Balfour HH Jr. Primary Epstein-Barr virus infection. J Clin Virol. 2018; 102:84-92. doi: 10.1016/j.jcv.2018.03.001.
Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W, et al.; International Human Genome Sequencing Consortium. Initial sequencing and analysis of the human genome. Nature. 2001; 409(6822):860-921. doi: 10.1038/35057062. Erratum in: Nature 2001; 412(6846):565. Erratum in: Nature 2001; 411(6838):720. Szustakowki, J [corrected to Szustakowski, J].
Garcia-Montojo M, Rodriguez-Martin E, Ramos-Mozo P, Ortega-Madueño I, Dominguez-Mozo MI, Arias-Leal A, García-Martínez MÁ, Casanova I, Galan V, Arroyo R, Álvarez-Lafuente R, Villar LM. Syncytin-1/HERV-W envelope is an early activation marker of leukocytes and is upregulated in multiple sclerosis patients. Eur J Immunol. 2020; 50(5):685-694. doi: 10.1002/eji.201948423.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2023 Aleksandra Ołownia, Jakub Orczyk, Małgorzata Kozioł
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The periodical offers access to content in the Open Access system under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0
Stats
Number of views and downloads: 571
Number of citations: 0