Epstein–Barr virus and multiple sclerosis

Authors

DOI:

https://doi.org/10.14739/2310-1237.2020.3.221870

Keywords:

Epstein–Barr virus, HHV-4, multiple sclerosis, demyelination, B lymphocytes, microglia

Abstract

 

Multiple sclerosis (MS) is a chronic inflammation of the central nervous system, a characteristic feature of which is the gradual development of focal and irreversible demyelination of the membranes of nerve structures in the spinal cord and brain, which leads to a gradual accumulation of neurological deficit and disability.

Aim – substantiation of the role of Epstein–Barr virus infection in the etiology and pathogenesis of MS based on the analysis of modern literary sources.

Herpes gamma viruses remain one of the most important suspects in the etiology of MS, including Epstein–Barr virus (EBV), which causes a lifelong infectious process in the human body. Human gammaherpesvirus 4 (HHV-4) can realize its pathogenic potential by performing lytic replication or lead to a delay in replication or reactivation of infection in both epithelial cells and B lymphocytes.

Taking into account current data on the biological properties of EBV and analyzing the role of this herpes virus in the pathogenesis of neurodegenerative diseases, this review was generated. Due to its molecular structure, EBV has specific biological properties, among which one of the most important is its tropism for the host’s immune tissue, in particular, B-lymphocytes, which obviously determines the life-long persistence of the virus. Thus, forming a latent process in the human body due to replicative cycles in B cells, EBV, on the one hand, controls the primary response of B lymphocytes, which leads to a deficiency of both humoral and cellular immunity factors. On the other hand, it contributes to the persistence of HHV-4 and the development of an infectious process constant with periods of reactivation.

With this in mind, an important detail that may link EBV infection with MS is that the development of the clinical picture and its course bears some similarity to natural HHV-4 infection, probably following the biological cycle of the virus over a certain period of time. Therefore, based on the found indirect relationship between EBV infection and MS, as well as on the indicated immunological and genetic mechanisms that are involved in neuroinflammatory processes, it is impossible not to take into account the role of herpes viruses in the development of the disease. But why, among a large population of HHV-4 carriers, only a small percentage develop EBV-associated MS remains to be seen.

Analyzing the conducted studies in which different results were obtained on the effect of EBV infection on different periods of MS development (by initiating the triggering or maintaining the inflammatory process or participating in its progression), it has now become clear that if the etiological role of EBV in this disease is present, then the course of the disease is not may not be related to HHV-4 biological cycles.

Conclusions. Currently, a direct connection is established between EBV infection and the development of MS. However, it is also impossible to refute and even more so to reject the role of human gammaherpesvirus 4 in the pathogenesis of multiple sclerosis.

References

Macaron, G., & Ontaneda, D. (2019). Diagnosis and Management of Progressive Multiple Sclerosis. Biomedicines, 7(3), 56. https://doi.org/10.3390/biomedicines7030056

Ontaneda, D., Fox, R. J., & Chataway, J. (2015). Clinical trials in progressive multiple sclerosis: lessons learned and future perspectives. The Lancet. Neurology, 14(2), 208-223. https://doi.org/10.1016/S1474-4422(14)70264-9

Belbasis, L., Bellou, V., Evangelou, E., Ioannidis, J. P., & Tzoulaki, I. (2015). Environmental risk factors and multiple sclerosis: an umbrella review of systematic reviews and meta-analyses. The Lancet. Neurology, 14(3), 263-273. https://doi.org/10.1016/S1474-4422(14)70267-4

Soldan, S. S., & Jacobson, S. (2016). Virus-Induced Demyelination: The Case for Virus(es) in Multiple Sclerosis. In: Neurotropic Viral Infections. Vol 2. Neurotropic Retroviruses, DNA Viruses, Immunity and Transmission (pp. 175-220). Springer International Publishing. https:// doi.org/10.1007/978-3-319-33189-8_6

Moreno, M. A., Or-Geva, N., Aftab, B. T., Khanna, R., Croze, E., Steinman, L., & Han, M. H. (2018). Molecular signature of Epstein-Barr virus infection in MS brain lesions. Neurology(R) neuroimmunology & neuroinflammation, 5(4), e466. https://doi.org/10.1212/NXI.0000000000000466

Bar-Or, A., Pender, M. P., Khanna, R., Steinman, L., Hartung, H. P., Maniar, T., Croze, E., Aftab, B. T., Giovannoni, G., & Joshi, M. A. (2020). Epstein-Barr Virus in Multiple Sclerosis: Theory and Emerging Immunotherapies. Trends in molecular medicine, 26(3), 296-310. https://doi.org/10.1016/j.molmed.2019.11.003

Hedström, A. K., Huang, J., Michel, A., Butt, J., Brenner, N., Hillert, J., Waterboer, T., Kockum, I., Olsson, T., & Alfredsson, L. (2020). High Levels of Epstein-Barr Virus Nuclear Antigen-1-Specific Antibodies and Infectious Mononucleosis Act Both Independently and Synergistically to Increase Multiple Sclerosis Risk. Frontiers in neurology, 10, 1368. https://doi.org/10.3389/fneur.2019.01368

Hecker, M., Fitzner, B., Wendt, M., Lorenz, P., Flechtner, K., Steinbeck, F., Schröder, I., Thiesen, H. J., & Zettl, U. K. (2016). High-Density Peptide Microarray Analysis of IgG Autoantibody Reactivities in Serum and Cerebrospinal Fluid of Multiple Sclerosis Patients. Molecular & cellular proteomics, 15(4), 1360-1380. https://doi.org/10.1074/mcp.M115.051664

Gieß, R. M., Pfuhl, C., Behrens, J. R., Rasche, L., Freitag, E., Khalighy, N., Otto, C., Wuerfel, J., Brandt, A. U., Hofmann, J., Eberspächer, B., Bellmann-Strobl, J., Paul, F., & Ruprecht, K. (2017). Epstein-Barr virus antibodies in serum and DNA load in saliva are not associated with radiological or clinical disease activity in patients with early multiple sclerosis. PloS one, 12(4), e0175279. https://doi.org/10.1371/journal.pone.0175279

Majerciak, V., Yang, W., Zheng, J., Zhu, J., & Zheng, Z. M. (2019). A Genome-Wide Epstein-Barr Virus Polyadenylation Map and Its Antisense RNA to EBNA. Journal of virology, 93(2), e01593-18. https://doi.org/10.1128/JVI.01593-18

Guan, Y., Jakimovski, D., Ramanathan, M., Weinstock-Guttman, B., & Zivadinov, R. (2019). The role of Epstein-Barr virus in multiple sclerosis: from molecular pathophysiology to in vivo imaging. Neural regeneration research, 14(3), 373-386. https://doi.org/10.4103/1673-5374.245462

Hassani, A., Corboy, J. R., Al-Salam, S., & Khan, G. (2018). Epstein-Barr virus is present in the brain of most cases of multiple sclerosis and may engage more than just B cells. PloS one, 13(2), e0192109. https://doi.org/10.1371/journal.pone.0192109

Möhl, B. S., Chen, J., Sathiyamoorthy, K., Jardetzky, T. S., & Longnecker, R. (2016). Structural and Mechanistic Insights into the Tropism of Epstein-Barr Virus. Molecules and cells, 39(4), 286-291. https://doi.org/10.14348/molcells.2016.0066

U.S. Department of Health & Human Services. (2018, May 10). Epstein-Barr Virus and Infectious Mononucleosis. Laboratory Testing. CDC. https://www.cdc.gov/epstein-barr/laboratory-testing.html

Styczynski, J., Tridello, G., Gil, L., Ljungman, P., Hoek, J., Iacobelli, S., Ward, K. N., Cordonnier, C., Einsele, H., Socie, G., Milpied, N., Veelken, H., Chevallier, P., Yakoub-Agha, I., Maertens, J., Blaise, D., Cornelissen, J., Michallet, M., Daguindau, E., Petersen, E., … Cesaro, S. (2016). Impact of Donor Epstein-Barr Virus Serostatus on the Incidence of Graft-Versus-Host Disease in Patients With Acute Leukemia After Hematopoietic Stem-Cell Transplantation: A Study From the Acute Leukemia and Infectious Diseases Working Parties of the European Society for Blood and Marrow Transplantation. Journal of clinical oncology, 34(19), 2212-2220. https://doi.org/10.1200/JCO.2015.64.2405

Kim, W. Y., Montes-Mojarro, I. A., Fend, F., & Quintanilla-Martinez, L. (2019). Epstein-Barr Virus-Associated T and NK-Cell Lymphoproliferative Diseases. Frontiers in pediatrics, 7, 71. https://doi.org/10.3389/fped.2019.00071

Mechelli, R., Manzari, C., Policano, C., Annese, A., Picardi, E., Umeton, R., Fornasiero, A., D'Erchia, A. M., Buscarinu, M. C., Agliardi, C., Annibali, V., Serafini, B., Rosicarelli, B., Romano, S., Angelini, D. F., Ricigliano, V A., Buttari, F., Battistini, L., Centonze, D., Guerini, F. R., … Ristori, G. (2015). Epstein-Barr virus genetic variants are associated with multiple sclerosis. Neurology, 84(13), 1362-1368. https://doi.org/10.1212/WNL.0000000000001420

Dunmire, S. K., Hogquist, K. A., & Balfour, H. H. (2015). Infectious Mononucleosis. Current topics in microbiology and immunology, 390(Pt 1), 211-240. https://doi.org/10.1007/978-3-319-22822-8_9

Rostgaard, K., Balfour, H. H., Jr, Jarrett, R., Erikstrup, C., Pedersen, O., Ullum, H., Nielsen, L. P., Voldstedlund, M., & Hjalgrim, H. (2019). Primary Epstein-Barr virus infection with and without infectious mononucleosis. PloS one, 14(12), e0226436. https://doi.org/10.1371/journal.pone.0226436

Aslan, N., Watkin, L. B., Gil, A., Mishra, R., Clark, F. G., Welsh, R. M., Ghersi, D., Luzuriaga, K., & Selin, L. K. (2017). Severity of Acute Infectious Mononucleosis Correlates with Cross-Reactive Influenza CD8 T-Cell Receptor Repertoires. mBio, 8(6), e01841-17. https://doi.org/10.1128/mBio.01841-17

Pender, M. P., Csurhes, P. A., Burrows, J. M., & Burrows, S. R. (2017). Defective T-cell control of Epstein-Barr virus infection in multiple sclerosis. Clinical & translational immunology, 6(1), e126. https://doi.org/10.1038/cti.2016.87

Otto, C., Hofmann, J., & Ruprecht, K. (2016). Antibody producing B lineage cells invade the central nervous system predominantly at the time of and triggered by acute Epstein-Barr virus infection: A hypothesis on the origin of intrathecal immunoglobulin synthesis in multiple sclerosis. Medical hypotheses, 91, 109-113. https://doi.org/10.1016/j.mehy.2016.04.025

Levin, L. I., Munger, K. L., O'Reilly, E. J., Falk, K. I., & Ascherio, A. (2010). Primary infection with the Epstein-Barr virus and risk of multiple sclerosis. Annals of neurology, 67(6), 824-830. https://doi.org/10.1002/ana.21978

Munger, K. L., Levin, L. I., O'Reilly, E. J., Falk, K. I., & Ascherio, A. (2011). Anti-Epstein-Barr virus antibodies as serological markers of multiple sclerosis: a prospective study among United States military personnel. Multiple sclerosis, 17(10), 1185-1193. https://doi.org/10.1177/1352458511408991

Kuhle, J., Disanto, G., Dobson, R., Adiutori, R., Bianchi, L., Topping, J., Bestwick, J. P., Meier, U. C., Marta, M., Dalla Costa, G., Runia, T., Evdoshenko, E., Lazareva, N., Thouvenot, E., Iaffaldano, P., Direnzo, V., Khademi, M., Piehl, F., Comabella, M., Sombekke, M., … Giovannoni, G. (2015). Conversion from clinically isolated syndrome to multiple sclerosis: A large multicentre study. Multiple sclerosis, 21(8), 1013-1024. https://doi.org/10.1177/1352458514568827

Huss, A. M., Halbgebauer, S., Öckl, P., Trebst, C., Spreer, A., Borisow, N., Harrer, A., Brecht, I., Balint, B., Stich, O., Schlegel, S., Retzlaff, N., Winkelmann, A., Roesler, R., Lauda, F., Yildiz, Ö., Voß, E., Muche, R., Rauer, S., Bergh, F. T., … Tumani, H. (2016). Importance of cerebrospinal fluid analysis in the era of McDonald 2010 criteria: a German-Austrian retrospective multicenter study in patients with a clinically isolated syndrome. Journal of neurology, 263(12), 2499-2504. https://doi.org/10.1007/s00415-016-8302-1

Dobson, R., Kuhle, J., Middeldorp, J., & Giovannoni, G. (2017). Epstein-Barr-negative MS: a true phenomenon?. Neurology(R) neuroimmunology & neuroinflammation, 4(2), e318. https://doi.org/10.1212/NXI.0000000000000318

Schwenkenbecher, P., Wurster, U., Konen, F. F., Gingele, S., Sühs, K. W., Wattjes, M. P., Stangel, M., & Skripuletz, T. (2019). Impact of the McDonald Criteria 2017 on Early Diagnosis of Relapsing-Remitting Multiple Sclerosis. Frontiers in neurology, 10, 188. https://doi.org/10.3389/fneur.2019.00188

Horakova, D., Zivadinov, R., Weinstock-Guttman, B., Havrdova, E., Qu, J., Tamaño-Blanco, M., Badgett, D., Tyblova, M., Bergsland, N., Hussein, S., Willis, L., Krasensky, J., Vaneckova, M., Seidl, Z., Lelkova, P., Dwyer, M. G., Zhang, M., Yu, H., Duan, X., Kalincik, T., … Ramanathan, M. (2013). Environmental factors associated with disease progression after the first demyelinating event: results from the multi-center SET study. PloS one, 8(1), e53996. https://doi.org/10.1371/journal.pone.0053996

Munger, K. L., Fitzgerald, K. C., Freedman, M. S., Hartung, H. P., Miller, D. H., Montalbán, X., Edan, G., Barkhof, F., Suarez, G., Radue, E. W., Sandbrink, R., Kappos, L., Pohl, C., & Ascherio, A. (2015). No association of multiple sclerosis activity and progression with EBV or tobacco use in BENEFIT. Neurology, 85(19), 1694-1701. https://doi.org/10.1212/WNL.0000000000002099

Deeba, E., Koptides, D., Gaglia, E., Constantinou, A., Lambrianides, A., Pantzaris, M., Krashias, G., & Christodoulou, C. (2019). Evaluation of Epstein-Barr virus-specific antibodies in Cypriot multiple sclerosis patients. Molecular immunology, 105, 270-275. https://doi.org/10.1016/j.molimm.2018.12.010

Sisay, S., Lopez-Lozano, L., Mickunas, M., Quiroga-Fernández, A., Palace, J., Warnes, G., Alvarez-Lafuente, R., Dua, P., & Meier, U. C. (2017). Untreated relapsing remitting multiple sclerosis patients show antibody production against latent Epstein Barr Virus (EBV) antigens mainly in the periphery and innate immune IL-8 responses preferentially in the CNS. Journal of neuroimmunology, 306, 40-45. https://doi.org/10.1016/j.jneuroim.2017.02.017

Almohmeed, Y. H., Avenell, A., Aucott, L., & Vickers, M. A. (2013). Systematic review and meta-analysis of the sero-epidemiological association between Epstein Barr virus and multiple sclerosis. PloS one, 8(4), e61110. https://doi.org/10.1371/journal.pone.0061110

Zivadinov, R., Cerza, N., Hagemeier, J., Carl, E., Badgett, D., Ramasamy, D. P., Weinstock-Guttman, B., & Ramanathan, M. (2016). Humoral response to EBV is associated with cortical atrophy and lesion burden in patients with MS. Neurology(R) neuroimmunology & neuroinflammation, 3(1), e190. https://doi.org/10.1212/NXI.0000000000000190

Castellazzi, M., Contini, C., Tamborino, C., Fasolo, F., Roversi, G., Seraceni, S., Rizzo, R., Baldi, E., Tola, M. R., Bellini, T., Granieri, E., & Fainardi, E. (2014). Epstein-Barr virus-specific intrathecal oligoclonal IgG production in relapsing-remitting multiple sclerosis is limited to a subset of patients and is composed of low-affinity antibodies. Journal of neuroinflammation, 11, 188. https://doi.org/10.1186/s12974-014-0188-1

Ruprecht, K., Wildemann, B., & Jarius, S. (2018). Low intrathecal antibody production despite high seroprevalence of Epstein-Barr virus in multiple sclerosis: a review of the literature. Journal of neurology, 265(2), 239-252. https://doi.org/10.1007/s00415-017-8656-z

Brändle, S. M., Obermeier, B., Senel, M., Bruder, J., Mentele, R., Khademi, M., Olsson, T., Tumani, H., Kristoferitsch, W., Lottspeich, F., Wekerle, H., Hohlfeld, R., & Dornmair, K. (2016). Distinct oligoclonal band antibodies in multiple sclerosis recognize ubiquitous self-proteins. Proceedings of the National Academy of Sciences of the United States of America, 113(28), 7864-7869. https://doi.org/10.1073/pnas.1522730113

Afrasiabi, A., Parnell, G. P., Fewings, N., Schibeci, S. D., Basuki, M. A., Chandramohan, R., Zhou, Y., Taylor, B., Brown, D. A., Swaminathan, S., McKay, F. C., Stewart, G. J., & Booth, D. R. (2019). Evidence from genome wide association studies implicates reduced control of Epstein-Barr virus infection in multiple sclerosis susceptibility. Genome medicine, 11(1), 26. https://doi.org/10.1186/s13073-019-0640-z

Tengvall, K., Huang, J., Hellström, C., Kammer, P., Biström, M., Ayoglu, B., Lima Bomfim, I., Stridh, P., Butt, J., Brenner, N., Michel, A., Lundberg, K., Padyukov, L., Lundberg, I. E., Svenungsson, E., Ernberg, I., Olafsson, S., Dilthey, A. T., Hillert, J., Alfredsson, L., … Kockum, I. (2019). Molecular mimicry between Anoctamin 2 and Epstein-Barr virus nuclear antigen 1 associates with multiple sclerosis risk. Proceedings of the National Academy of Sciences of the United States of America, 116(34), 16955-16960. https://doi.org/10.1073/pnas.1902623116

Baranzini, S. E., & Oksenberg, J. R. (2017). The Genetics of Multiple Sclerosis: From 0 to 200 in 50 Years. Trends in genetics, 33(12), 960-970. https://doi.org/10.1016/j.tig.2017.09.004

Kular, L., Liu, Y., Ruhrmann, S., Zheleznyakova, G., Marabita, F., Gomez-Cabrero, D., James, T., Ewing, E., Lindén, M., Górnikiewicz, B., Aeinehband, S., Stridh, P., Link, J., Andlauer, T., Gasperi, C., Wiendl, H., Zipp, F., Gold, R., Tackenberg, B., Weber, F., … Jagodic, M. (2018). DNA methylation as a mediator of HLA-DRB1*15:01 and a protective variant in multiple sclerosis. Nature communications, 9(1), 2397. https://doi.org/10.1038/s41467-018-04732-5

Stürner, K. H., Siembab, I., Schön, G., Stellmann, J. P., Heidari, N., Fehse, B., Heesen, C., Eiermann, T. H., Martin, R., & Binder, T. M. (2019). Is multiple sclerosis progression associated with the HLA-DR15 haplotype?. Multiple sclerosis journal - experimental, translational and clinical, 5(4), 2055217319894615. https://doi.org/10.1177/2055217319894615

Agostini, S., Mancuso, R., Guerini, F. R., D'Alfonso, S., Agliardi, C., Hernis, A., Zanzottera, M., Barizzone, N., Leone, M. A., Caputo, D., Rovaris, M., & Clerici, M. (2018). HLA alleles modulate EBV viral load in multiple sclerosis. Journal of translational medicine, 16(1), 80. https://doi.org/10.1186/s12967-018-1450-6

Moutsianas, L., Jostins, L., Beecham, A. H., Dilthey, A. T., Xifara, D. K., Ban, M., Shah, T. S., Patsopoulos, N. A., Alfredsson, L., Anderson, C. A., Attfield, K. E., Baranzini, S. E., Barrett, J., Binder, T., Booth, D., Buck, D., Celius, E. G., Cotsapas, C., D'Alfonso, S., Dendrou, C. A., … McVean, G. (2015). Class II HLA interactions modulate genetic risk for multiple sclerosis. Nature genetics, 47(10), 1107-1113. https://doi.org/10.1038/ng.3395

Hollenbach, J. A., & Oksenberg, J. R. (2015). The immunogenetics of multiple sclerosis: A comprehensive review. Journal of autoimmunity, 64, 13-25. https://doi.org/10.1016/j.jaut.2015.06.010

Serafini, B., Rosicarelli, B., Veroni, C., Mazzola, G. A., & Aloisi, F. (2019). Epstein-Barr Virus-Specific CD8 T Cells Selectively Infiltrate the Brain in Multiple Sclerosis and Interact Locally with Virus-Infected Cells: Clue for a Virus-Driven Immunopathological Mechanism. Journal of virology, 93(24), e00980-19. https://doi.org/10.1128/JVI.00980-19

Xiao, D., Ye, X., Zhang, N., Ou, M., Guo, C., Zhang, B., Liu, Y., Wang, M., Yang, G., & Jing, C. (2015). A meta-analysis of interaction between Epstein-Barr virus and HLA-DRB1*1501 on risk of multiple sclerosis. Scientific reports, 5, 18083. https://doi.org/10.1038/srep18083

Tschochner, M., Leary, S., Cooper, D., Strautins, K., Chopra, A., Clark, H., Choo, L., Dunn, D., James, I., Carroll, W. M., Kermode, A. G., & Nolan, D. (2016). Identifying Patient-Specific Epstein-Barr Nuclear Antigen-1 Genetic Variation and Potential Autoreactive Targets Relevant to Multiple Sclerosis Pathogenesis. PloS one, 11(2), e0147567. https://doi.org/10.1371/journal.pone.0147567

Hojati Z. (2017). Molecular Genetic and Epigenetic Basis of Multiple Sclerosis. Advances in experimental medicine and biology, 958, 65-90. https://doi.org/10.1007/978-3-319-47861-6_6

Celarain, N., & Tomas-Roig, J. (2020). Aberrant DNA methylation profile exacerbates inflammation and neurodegeneration in multiple sclerosis patients. Journal of neuroinflammation, 17(1), 21. https://doi.org/10.1186/s12974-019-1667-1

Lassmann H. (2014). Mechanisms of white matter damage in multiple sclerosis. Glia, 62(11), 1816-1830. https://doi.org/10.1002/glia.22597

Guerrero, B. L., & Sicotte, N. L. (2020). Microglia in Multiple Sclerosis: Friend or Foe?. Frontiers in immunology, 11, 374. https://doi.org/10.3389/fimmu.2020.00374

Forrest, C., Hislop, A. D., Rickinson, A. B., & Zuo, J. (2018). Proteome-wide analysis of CD8+ T cell responses to EBV reveals differences between primary and persistent infection. PLoS pathogens, 14(9), e1007110. https://doi.org/10.1371/journal.ppat.1007110

Michel, L., Touil, H., Pikor, N. B., Gommerman, J. L., Prat, A., & Bar-Or, A. (2015). B Cells in the Multiple Sclerosis Central Nervous System: Trafficking and Contribution to CNS-Compartmentalized Inflammation. Frontiers in immunology, 6, 636. https://doi.org/10.3389/fimmu.2015.00636

Nemecek, A., Zimmermann, H., Rübenthaler, J., Fleischer, V., Paterka, M., Luessi, F., Müller-Forell, W., Zipp, F., & Siffrin, V. (2016). Flow cytometric analysis of T cell/monocyte ratio in clinically isolated syndrome identifies patients at risk of rapid disease progression. Multiple sclerosis, 22(4), 483-493. https://doi.org/10.1177/1352458515593821

Labzin, L. I., Heneka, M. T., & Latz, E. (2018). Innate Immunity and Neurodegeneration. Annual review of medicine, 69, 437-449. https://doi.org/10.1146/annurev-med-050715-104343

Prinz, M., Erny, D., & Hagemeyer, N. (2017). Ontogeny and homeostasis of CNS myeloid cells. Nature immunology, 18(4), 385-392. https://doi.org/10.1038/ni.3703

O'Loughlin, E., Madore, C., Lassmann, H., & Butovsky, O. (2018). Microglial Phenotypes and Functions in Multiple Sclerosis. Cold Spring Harbor perspectives in medicine, 8(2), a028993. https://doi.org/10.1101/cshperspect.a028993

Baufeld, C., O'Loughlin, E., Calcagno, N., Madore, C., & Butovsky, O. (2018). Differential contribution of microglia and monocytes in neurodegenerative diseases. Journal of neural transmission, 125(5), 809-826. https://doi.org/10.1007/s00702-017-1795-7

Miron, V. E., Boyd, A., Zhao, J. W., Yuen, T. J., Ruckh, J. M., Shadrach, J. L., van Wijngaarden, P., Wagers, A. J., Williams, A., Franklin, R., & Ffrench-Constant, C. (2013). M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination. Nature neuroscience, 16(9), 1211-1218. https://doi.org/10.1038/nn.3469

Zrzavy, T., Hametner, S., Wimmer, I., Butovsky, O., Weiner, H. L., & Lassmann, H. (2017). Loss of 'homeostatic' microglia and patterns of their activation in active multiple sclerosis. Brain, 140(7), 1900-1913. https://doi.org/10.1093/brain/awx113

van Wageningen, T. A., Vlaar, E., Kooij, G., Jongenelen, C., Geurts, J., & van Dam, A. M. (2019). Regulation of microglial TMEM119 and P2RY12 immunoreactivity in multiple sclerosis white and grey matter lesions is dependent on their inflammatory environment. Acta neuropathologica communications, 7(1), 206. https://doi.org/10.1186/s40478-019-0850-z

Guillot-Sestier, M. V., & Town, T. (2018). Let's make microglia great again in neurodegenerative disorders. Journal of neural transmission, 125(5), 751-770. https://doi.org/10.1007/s00702-017-1792-x

Mammana, S., Fagone, P., Cavalli, E., Basile, M. S., Petralia, M. C., Nicoletti, F., Bramanti, P., & Mazzon, E. (2018). The Role of Macrophages in Neuroinflammatory and Neurodegenerative Pathways of Alzheimer's Disease, Amyotrophic Lateral Sclerosis, and Multiple Sclerosis: Pathogenetic Cellular Effectors and Potential Therapeutic Targets. International journal of molecular sciences, 19(3), 831. https://doi.org/10.3390/ijms19030831

Roy Sarkar, S., & Banerjee, S. (2019). Gut microbiota in neurodegenerative disorders. Journal of neuroimmunology, 328, 98-104. https://doi.org/10.1016/j.jneuroim.2019.01.004

Sherwin, E., Dinan, T. G., & Cryan, J. F. (2018). Recent developments in understanding the role of the gut microbiota in brain health and disease. Annals of the New York Academy of Sciences, 1420(1), 5-25. https://doi.org/10.1111/nyas.13416

Brooks, J. M., Long, H. M., Tierney, R. J., Shannon-Lowe, C., Leese, A. M., Fitzpatrick, M., Taylor, G. S., & Rickinson, A. B. (2016). Early T Cell Recognition of B Cells following Epstein-Barr Virus Infection: Identifying Potential Targets for Prophylactic Vaccination. PLoS pathogens, 12(4), e1005549. https://doi.org/10.1371/journal.ppat.1005549

Cohen J. I. (2018). Vaccine Development for Epstein-Barr Virus. Advances in experimental medicine and biology, 1045, 477-493. https://doi.org/10.1007/978-981-10-7230-7_22

How to Cite

1.
Skliar AI, Torianyk II, Osolodchenko TP, Ponomarenko SV. Epstein–Barr virus and multiple sclerosis. Pathologia [Internet]. 2020Dec.29 [cited 2024Mar.28];(3). Available from: http://pat.zsmu.edu.ua/article/view/221870

Issue

Section

Review