van de Waterweg Berends, Annet Francien ; Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) > FARAH: Santé publique vétérinaire ; Neuro-Immune Connections and Repair Lab, Biomedical Research Institute, Department of Immunology and Infection, UHasselt, Diepenbeek, Belgium ; University MS Center, Campus Diepenbeek, Diepenbeek, Belgium
Broux, B; Neuro-Immune Connections and Repair Lab, Biomedical Research Institute, Department of Immunology and Infection, UHasselt, Diepenbeek, Belgium ; University MS Center, Campus Diepenbeek, Diepenbeek, Belgium
Machiels, Bénédicte ; Université de Liège - ULiège > Département des maladies infectieuses et parasitaires (DMI) > Vaccinologie vétérinaire
Gillet, Laurent ; Université de Liège - ULiège > Département des maladies infectieuses et parasitaires (DMI) > Vaccinologie vétérinaire
Hellings, N; Neuro-Immune Connections and Repair Lab, Biomedical Research Institute, Department of Immunology and Infection, UHasselt, Diepenbeek, Belgium ; University MS Center, Campus Diepenbeek, Diepenbeek, Belgium
F.R.S.-FNRS - Fonds de la Recherche Scientifique Belgian Charcot Foundation
Funding text :
The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Our research on EBV and MS is funded by the Belgian Charcot Foundation, the Flemish Research Foundation (FWO), and the National Fund of Scientific Research (FNRS).
Huang J Kockum I Stridh P. Trends in the environmental risks associated with earlier onset in multiple sclerosis. Multiple Sclerosis Related Disord. (2022) 68:104250. doi: 10.1016/j.msard.2022.104250
Warner HB Carp RI. Multiple Sclerosis etiology — an Epstein-Barr virus hypothesis. Med Hypotheses. (1988) 25:93–7. doi: 10.1016/0306-9877(88)90024-2
Angelini DF Serafini B Piras E Severa M Coccia EM Rosicarelli B et al. Increased CD8+ T cell response to Epstein-Barr virus lytic antigens in the active phase of multiple sclerosis. PloS Pathog. (2013) 9:e1003220. doi: 10.1371/journal.ppat.1003220
Ascherio A Munger KL Lennette ET Spiegelman D Hernán MA Olek MJ et al. Epstein-Barr virus antibodies and risk of multiple sclerosis: a prospective study. Jama. (2001) 286:3083–8. doi: 10.1001/jama.286.24.3083
Abdelrahman HS Selim HS Hashish MH Sultan LI. Epstein-Barr virus in multiple sclerosis. J Egypt Public Health Assoc. (2014) 89:90–5. doi: 10.1097/01.EPX.0000452287.65133.fc
Farrell RA Antony D Wall GR Clark DA Fisniku L Swanton J et al. Humoral immune response to EBV in multiple sclerosis is associated with disease activity on MRI. Neurology. (2009) 73:32–8. doi: 10.1212/WNL.0b013e3181aa29fe
Dobson R Kuhle J Middeldorp J Giovannoni G. Epstein-Barr-negative MS: a true phenomenon? Neurol Neuroimmunol Neuroinflamm. (2017) 4:e318. doi: 10.1212/NXI.0000000000000318
Balfour HH Jr.Odumade OA Schmeling DO Mullan BD Ed JA Knight JA et al. Behavioral, virologic, and immunologic factors associated with acquisition and severity of primary Epstein-Barr virus infection in university students. J Infect Dis. (2013) 207:80–8. doi: 10.1093/infdis/jis646
Kuri A Jacobs BM Vickaryous N Pakpoor J Middeldorp J Giovannoni G et al. Epidemiology of Epstein-Barr virus infection and infectious mononucleosis in the United Kingdom. BMC Public Health. (2020) 20:912. doi: 10.1186/s12889-020-09049-x
Thacker EL Mirzaei F Ascherio A. Infectious mononucleosis and risk for multiple sclerosis: a meta-analysis. Ann Neurol. (2006) 59:499–503. doi: 10.1002/ana.20820
Nielsen TR Rostgaard K Nielsen NM Koch-Henriksen N Haahr S Sørensen PS et al. Multiple sclerosis after infectious mononucleosis. Arch Neurol. (2007) 64:72–5. doi: 10.1001/archneur.64.1.72
Trottier H Buteau C Robitaille N Duval M Tucci M Lacroix J et al. Transfusion-related Epstein-Barr virus infection among stem cell transplant recipients: a retrospective cohort study in children. Transfusion. (2012) 52:2653–63. doi: 10.1111/j.1537-2995.2012.03611.x
Papesch M Watkins R. Epstein-Barr virus infectious mononucleosis. Clin Otolaryngol Allied Sci. (2001) 26:3–8. doi: 10.1046/j.1365-2273.2001.00431.x
Munk Nielsen N Corn G Frisch M Stenager E Koch-Henriksen N Wohlfahrt J et al. Multiple sclerosis among first- and second-generation immigrants in Denmark: a population-based cohort study. Brain. (2019) 142:1587–97. doi: 10.1093/brain/awz088
Compston A Confavreux C. Compston A Confavreux C Lassmann H McDonald I Miller D Noseworthy J et al. editors. McAlpine’s Multiple Sclerosis, 4th ed. Churchill Livingstone, Edinburgh (2006). 71–111.
Gale CR Martyn CN. Migrant studies in multiple sclerosis. Prog Neurobiol. (1995) 47:425–48. doi: 10.1016/0301-0082(95)80008-V
Bjornevik K Cortese M Healy BC Kuhle J Mina MJ Leng Y et al. Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis. Science. (2022) 375:296–301. doi: 10.1126/science.abj8222
Goldacre R. Risk of multiple sclerosis in individuals with infectious mononucleosis: a national population-based cohort study using hospital records in England, 2003-2023. Mult Scler. (2024) 30:489–95. doi: 10.1177/13524585241237707
Xu Y Hiyoshi A Smith KA Piehl F Olsson T Fall K et al. Association of infectious mononucleosis in childhood and adolescence with risk for a subsequent multiple sclerosis diagnosis among siblings. JAMA Netw Open. (2021) 4:e2124932. doi: 10.1001/jamanetworkopen.2021.24932
Banwell B Krupp L Kennedy J Tellier R Tenembaum S Ness J et al. Clinical features and viral serologies in children with multiple sclerosis: a multinational observational study. Lancet Neurol. (2007) 6:773–81. doi: 10.1016/S1474-4422(07)70196-5
Nourbakhsh B Cordano C Asteggiano C Ruprecht K Otto C Rutatangwa A et al. Multiple sclerosis is rare in epstein-barr virus-seronegative children with central nervous system inflammatory demyelination. Ann Neurol. (2021) 89:1234–9. doi: 10.1002/ana.26062
Robinson WH Steinman L. Epstein-Barr virus and multiple sclerosis. Science. (2022) 375:264–5. doi: 10.1126/science.abm7930
Soldan SS Lieberman PM. Epstein-Barr virus and multiple sclerosis. Nat Rev Microbiol. (2023) 21:51–64. doi: 10.1038/s41579-022-00770-5
Vietzen H Berger SM Kühner LM Furlano PL Bsteh G Berger T et al. Ineffective control of Epstein-Barr-virus-induced autoimmunity increases the risk for multiple sclerosis. Cell. (2023) 186:5705–18.e13. doi: 10.1016/j.cell.2023.11.015
Cossu D Tomizawa Y Sechi LA Hattori N. Epstein–barr virus and human endogenous retrovirus in Japanese patients with autoimmune demyelinating disorders. Int J Mol Sci. (2023) 24:17151. doi: 10.3390/ijms242417151
Meier UC Cipian RC Karimi A Ramasamy R Middeldorp JM. Cumulative roles for epstein-barr virus, human endogenous retroviruses, and human herpes virus-6 in driving an inflammatory cascade underlying MS pathogenesis. Front Immunol. (2021) 12:757302. doi: 10.3389/fimmu.2021.757302
Antony JM van Marle G Opii W Butterfield DA Mallet F Yong VW et al. Human endogenous retrovirus glycoprotein-mediated induction of redox reactants causes oligodendrocyte death and demyelination. Nat Neurosci. (2004) 7:1088–95. doi: 10.1038/nn1319
Censi ST Mariani-Costantini R Granzotto A Tomassini V Sensi SL. Endogenous retroviruses in multiple sclerosis: A network-based etiopathogenic model. Ageing Res Rev. (2024) 99:102392. doi: 10.1016/j.arr.2024.102392
Grut V Biström M Salzer J Stridh P Jons D Gustafsson R et al. Cytomegalovirus seropositivity is associated with reduced risk of multiple sclerosis-a presymptomatic case-control study. Eur J Neurol. (2021) 28:3072–9. doi: 10.1111/ene.14961
Maple PAC Tanasescu R Gran B Constantinescu CS. A different response to cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infection in UK people with multiple sclerosis (PwMS) compared to controls. J Infect. (2020) 80:320–5. doi: 10.1016/j.jinf.2019.10.017
Márquez AC Croft C Shanina I Horwitz MS. Influence of type I interferons in gammaherpesvirus-68 and its influence on EAE enhancement. Front Immunol. (2022) 13:858583. doi: 10.3389/fimmu.2022.858583
Casiraghi C Shanina I Cho S Freeman ML Blackman MA Horwitz MS. Gammaherpesvirus latency accentuates EAE pathogenesis: relevance to Epstein-Barr virus and multiple sclerosis. PloS Pathog. (2012) 8:e1002715. doi: 10.1371/journal.ppat.1002715
Flaño E Woodland DL Blackman MA. A mouse model for infectious mononucleosis. Immunol Res. (2002) 25:201–17. doi: 10.1385/IR:25:3
Virgin H Latreille P Wamsley P Hallsworth K Weck KE Dal Canto AJ et al. Complete sequence and genomic analysis of murine gammaherpesvirus 68. J Virol. (1997) 71:5894–904. doi: 10.1128/jvi.71.8.5894-5904.1997
Zdimerova H Murer A Engelmann C Raykova A Deng Y Gujer C et al. Attenuated immune control of Epstein-Barr virus in humanized mice is associated with the multiple sclerosis risk factor HLA-DR15. Eur J Immunol. (2021) 51:64–75. doi: 10.1002/eji.202048655
Münz C. EBV infection of mice with reconstituted human immune system components. Curr Top Microbiol Immunol. (2015) 391:407–23. doi: 10.1007/978-3-319-22834-1_14
Sokal EM Hoppenbrouwers K Vandermeulen C Moutschen M Léonard P Moreels A et al. Recombinant gp350 vaccine for infectious mononucleosis: a phase 2, randomized, double-blind, placebo-controlled trial to evaluate the safety, immunogenicity, and efficacy of an Epstein-Barr virus vaccine in healthy young adults. J Infect Dis. (2007) 196:1749–53. doi: 10.1086/523813
Dourcy M Maquet C Dams L Gilliaux G Javaux J Desmecht D et al. A gammaherpesvirus licenses CD8 T cells to protect the host from pneumovirus-induced immunopathologies. Mucosal Immunol. (2020) 13:799–813. doi: 10.1038/s41385-020-0293-7
Barton ES White DW Cathelyn JS Brett-McClellan KA Engle M Diamond MS et al. Herpesvirus latency confers symbiotic protection from bacterial infection. Nature. (2007) 447:326–9. doi: 10.1038/nature05762
Machiels B Dourcy M Xiao X Javaux J Mesnil C Sabatel C et al. A gammaherpesvirus provides protection against allergic asthma by inducing the replacement of resident alveolar macrophages with regulatory monocytes. Nat Immunol. (2017) 18:1310–20. doi: 10.1038/ni.3857
Moyano A Ferressini Gerpe NM De Matteo E Preciado MV Chabay P. M1 macrophage polarization prevails in epstein-barr virus-infected children in an immunoregulatory environment. J Virol. (2022) 96:e0143421. doi: 10.1128/JVI.01434-21
Wang J Su M Wei N Yan H Zhang J Gong Y et al. Chronic active epstein-barr virus disease originates from infected hematopoietic stem cells. Blood. (2023) 143:32–41. doi: 10.1182/blood-2023-173226
Indari O Chandramohanadas R Jha HC. Epstein-Barr virus infection modulates blood-brain barrier cells and its co-infection with Plasmodium falciparum induces RBC adhesion. Pathog Dis. (2021) 79:ftaa080. doi: 10.1093/femspd/ftaa080
