nnpNeurology, Neuropsychiatry, PsychosomaticsНеврология, нейропсихиатрия, психосоматика2074-27112310-1342"IMA-Press", LLC10.14412/2074-2711-2026-2-93-100nnp-2821Research ArticleREVIEWSОБЗОРЫHuman herpesvirus 6A and other risk factors for multiple sclerosisВирус герпеса человека 6А и другие факторы риска развития рассеянного склерозаhttps://orcid.org/0000-0003-0169-3956ХрулевА. Е.KhrulevA. E.

Алексей Евгеньевич Хрулев

603005; пл. Минина и Пожарского, 10/1; Нижний Новгород

Alexey Yevgenyevich Khrulev

603005; 10/1, Minina and Pozharskogo Sq.; Nizhny Novgorod

alexey_khrulev@mail.ruhttps://orcid.org/0009-0005-7693-0452ВанеевИ. Н.VaneevI. N.

603005; пл. Минина и Пожарского, 10/1; Нижний Новгород

603005; 10/1, Minina and Pozharskogo Sq.; Nizhny Novgorod

https://orcid.org/0000-0002-7571-525XУткинО. В.UtkinO. V.

603950; ул. Малая Ямская, 71; Нижний Новгород

603950; 71, Malaya Yamskaya St.; Nizhny Novgorod

https://orcid.org/0000-0002-6683-7191ФилатоваЕ. Н.FilatovaE. N.

603950; ул. Малая Ямская, 71; Нижний Новгород

603950; 71, Malaya Yamskaya St.; Nizhny Novgorod

https://orcid.org/0000-0003-0402-7430ШейкоГ. Е.SheikoG. E.

603005; пл. Минина и Пожарского, 10/1; Нижний Новгород

603005; 10/1, Minina and Pozharskogo Sq.; Nizhny Novgorod

https://orcid.org/0000-0001-9719-6772БеловаА. Н.BelovaA. N.

603005; пл. Минина и Пожарского, 10/1; Нижний Новгород

603005; 10/1, Minina and Pozharskogo Sq.; Nizhny Novgorod

https://orcid.org/0000-0002-2975-4151БойкоА. Н.BoykoA. N.

117997; ул. Островитянова, 1;  ул. Островитянова, 1, стр. 10; Москва

117997; 1, Ostrovityanova St.; 1, Ostrovityanova St., Build. 10; Moscow

ФГБОУ ВО «Приволжский исследовательский медицинский университет» Минздрава РоссииРоссияPrivolzhsky Research Medical University, Ministry of Health of RussiaRussian FederationФБУН «Нижегородский научно-исследовательский институт эпидемиологии и микробиологии им. акад. И.Н. Блохиной» РоспотребнадзораРоссияAcademician I.N. Blokhina Nizhny Novgorod Research Institute of Epidemiology and Microbiology, Federal Service for Surveillance on Consumer Rights Protection and Human WellbeingRussian FederationФГАОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России; ФГБУ «Федеральный центр мозга и нейротехнологий» ФМБА РоссииРоссияN.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia; Federal Center of Brain and Neurotechnologies, FMBA of RussiaRussian Federation20262404202618293100Copyright © Khrulev A.E., Vaneev I.N., Utkin O.V., Filatova E.N., Sheiko G.E., Belova A.N., Boyko A.N., 20262026Хрулев А.Е., Ванеев И.Н., Уткин О.В., Филатова Е.Н., Шейко Г.Е., Белова А.Н., Бойко А.Н.Khrulev A.E., Vaneev I.N., Utkin O.V., Filatova E.N., Sheiko G.E., Belova A.N., Boyko A.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://nnp.ima-press.net/nnp/article/view/2821

   Based on a review of the literature, this article summarises the findings of original studies on the role of human herpesvirus 6A (HHV-6A) in the development of multiple sclerosis (MS). The review also presents the immunological and pathogenetic rationale for the role of other viruses – Epstein–Barr virus (EBV) and human endogenous retrovirus-W (HERV-W) – in the development of MS. Experimental and clinical data on risk factors for the development of MS are examined in the context of the established presence of the aforementioned viruses in patients.

   Particular attention is paid to the role of HHV-6A as a potential trigger of the inflammatory autoimmune cascade in MS.

   Information on the possible role of the combination of HHV-6A with other viruses (co-infection) in the pathogenesis of MS is summarized and presented. In addition to the viral nature of MS development, the article focuses on endogenous (genetically determined) and other external factors.

   На основе анализа данных литературы обобщены результаты оригинальных исследований о роли вируса герпеса человека 6А (ВГЧ6А) в развитии рассеянного склероза (РС). Также в обзоре приводится иммунологическое и патогенетическое обоснование роли других вирусов: вируса Эпштейна–Барр (ВЭБ) и эндогенного ретровируса человека W (human endogenous retrovirus-W, HERV-W) – в развитии РС. Рассматриваются экспериментальные и клинические данные о факторах риска развития РС в контексте установленного факта наличия у пациентов вышеперечисленных вирусов.

   Особое внимание уделяется роли ВГЧ6А как потенциального триггера воспалительного аутоиммунного каскада при РС.

   Обобщены и представлены сведения о возможной роли сочетания ВГЧ6А с другими вирусами (коинфекция) в патогенезе РС. В статье помимо вирусной природы развития РС уделяется внимание эндогенным (генетически детерминированным) и другим внешним факторам.

вирус герпеса человека 6Авирус Эпштейна–Баррэндогенный ретровирус человека Wцитомегаловирусрассеянный склерозфакторы рискаhuman herpes virus 6AEpstein–Barr virushuman endogenous retrovirus-Wcytomegalovirusmultiple sclerosisrisk factorИсследование не имело спонсорской поддержкиThe investigation has not been sponsoredReferencesVitturi BK, Cellerino M, Boccia D, et al. Environmental risk factors for multiple sclerosis : a comprehensive systematic review and meta-analysis. J Neurol. 2025 Jul;272(8):513. doi: 10.1007/s00415-025-13248-0Vitturi BK, Cellerino M, Boccia D, et al. Environmental risk factors for multiple sclerosis : a comprehensive systematic review and meta-analysis. J Neurol. 2025 Jul;272(8):513. doi: 10.1007/s00415-025-13248-0Рубрикатор клинических рекомендаций Минздрава России. Доступно по ссылке: https://cr.minzdrav.gov.ru/view-cr/739_2 (дата обращения 01. 02. 2026).Clinical Guidelines of the Ministry of Health of Russia. Available at: https://cr.minzdrav.gov.ru/view-cr/739_2 (accessed 01. 02. 2026) (In Russ.).Belbasis L, Bellou V, Evangelou E, Tzoulaki I. Environmental factors and risk of multiple sclerosis: Findings from meta-analyses and Mendelian randomization studies. Mult Scler. 2020 Apr;26(4):397-404. doi: 10.1177/1352458519872664Belbasis L, Bellou V, Evangelou E, Tzoulaki I. Environmental factors and risk of multiple sclerosis: Findings from meta-analyses and Mendelian randomization studies. Mult Scler. 2020 Apr;26(4):397-404. doi: 10.1177/1352458519872664Dunn N, Kharlamova N, Fogdell-Hahn A. The role of herpesvirus 6A and 6B in multiple sclerosis and epilepsy. Scand J Immunol. 2020 Dec;92(6):e12984. doi: 10.1111/sji.12984Dunn N, Kharlamova N, Fogdell-Hahn A. The role of herpesvirus 6A and 6B in multiple sclerosis and epilepsy. Scand J Immunol. 2020 Dec;92(6):e12984. doi: 10.1111/sji.12984Pormohammad A, Azimi T, Falah F, Faghihloo E. Relationship of human herpes virus 6 and multiple sclerosis : A systematic review and meta-analysis. Cell Physiol. 2018 Apr;233(4):2850-62. doi: 10.1002/jcp.26000Pormohammad A, Azimi T, Falah F, Faghihloo E. Relationship of human herpes virus 6 and multiple sclerosis : A systematic review and meta-analysis. Cell Physiol. 2018 Apr;233(4):2850-62. doi: 10.1002/jcp.26000Caserta MT. Human Herpesvirus 6 Infection of the Central Nervous System. Curr Infect Dis Rep. 2004 Aug;6(4):316-21. doi: 10.1007/s11908-004-0054-xCaserta MT. Human Herpesvirus 6 Infection of the Central Nervous System. Curr Infect Dis Rep. 2004 Aug;6(4):316-21. doi: 10.1007/s11908-004-0054-xKostare G, Kostares E, Kostares M, et al. Prevalence of HHV-6 Detection Among People Living with HIV : A Systematic Review and Meta-Analysis. Viruses. 2025 Apr;17(4):531. doi: 10.3390/v17040531Kostare G, Kostares E, Kostares M, et al. Prevalence of HHV-6 Detection Among People Living with HIV : A Systematic Review and Meta-Analysis. Viruses. 2025 Apr;17(4):531. doi: 10.3390/v17040531ICTV Global. ICTV Global Taxonomy. International Committee on Taxonomy of Viruses. 2024. Available at: https://ictv.global/taxonomy/ICTV Global. ICTV Global Taxonomy. International Committee on Taxonomy of Viruses. 2024. Available at: https://ictv.global/taxonomy/Bartolini L, Theodore WH, Jacobson S, Gaillard WD. Infection with HHV-6 and its role in epilepsy. Epilepsy Res. 2019 Jul;153:34-9. doi: 10.1016/j.eplepsyres.2019.03.016Bartolini L, Theodore WH, Jacobson S, Gaillard WD. Infection with HHV-6 and its role in epilepsy. Epilepsy Res. 2019 Jul;153:34-9. doi: 10.1016/j.eplepsyres.2019.03.016Forni D, Cagliani R, Clerici M, et al. Evolutionary analysis of exogenous and integrated HHV-6A/HHV-6B populations. Virus Evol. 2020 Apr;6(1):veaa035. doi: 10.1093/ve/veaa035Forni D, Cagliani R, Clerici M, et al. Evolutionary analysis of exogenous and integrated HHV-6A/HHV-6B populations. Virus Evol. 2020 Apr;6(1):veaa035. doi: 10.1093/ve/veaa035Pellett PE, Ablashi DV, Ambros PF, et al. Chromosomally integrated human herpesvirus 6: questions and answers. Rev Med Virol. 2012 May;22(3):144-55. doi: 10.1002/rmv.715Pellett PE, Ablashi DV, Ambros PF, et al. Chromosomally integrated human herpesvirus 6: questions and answers. Rev Med Virol. 2012 May;22(3):144-55. doi: 10.1002/rmv.715Tarlinton RE, Martynova E, Rizvanov AA, et al. Role of Viruses in the Pathogenesis of Multiple Sclerosis. Viruses. 2020 Jun;12(6):643. doi: 10.3390/v12060643Tarlinton RE, Martynova E, Rizvanov AA, et al. Role of Viruses in the Pathogenesis of Multiple Sclerosis. Viruses. 2020 Jun;12(6):643. doi: 10.3390/v12060643Meier UC, Cipian RC, Karimi A, et al. 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 Nov;12:757302. doi: 10.3389/fimmu.2021.757302Meier UC, Cipian RC, Karimi A, et al. 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 Nov;12:757302. doi: 10.3389/fimmu.2021.757302Ballerini C, Amoriello R, Maghrebi O, et al. Exploring the role of EBV in multiple sclerosis pathogenesis through EBV interactome. Front Immunol. 2025 Apr;16:1557483. doi: 10.3389/fimmu.2025.1557483Ballerini C, Amoriello R, Maghrebi O, et al. Exploring the role of EBV in multiple sclerosis pathogenesis through EBV interactome. Front Immunol. 2025 Apr;16:1557483. doi: 10.3389/fimmu.2025.1557483Louveau A, Herz J, Alme MN, et al. CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature. Nat Neurosci. 2018 Oct;21(10):1380-91. doi: 10.1038/s41593-018-0227-9Louveau A, Herz J, Alme MN, et al. CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature. Nat Neurosci. 2018 Oct;21(10):1380-91. doi: 10.1038/s41593-018-0227-9Pender MP, Csurhes PA, Burrows JM, Burrows SR. Defective T-cell control of Epstein-Barr virus infection in multiple sclerosis. Clin Transl Immunol. 2017 Jan;6(1):e126. doi: 10.1038/cti.2016.87Pender MP, Csurhes PA, Burrows JM, Burrows SR. Defective T-cell control of Epstein-Barr virus infection in multiple sclerosis. Clin Transl Immunol. 2017 Jan;6(1):e126. doi: 10.1038/cti.2016.87Van Langelaar J, Rijvers L, Smolders J, van Luijn MM. B and T Cells Driving Multiple Sclerosis: Identity, Mechanisms and Potential Triggers. Front Immunol. 2020 May;11:760. doi: 10.3389/fimmu.2020.00760Van Langelaar J, Rijvers L, Smolders J, van Luijn MM. B and T Cells Driving Multiple Sclerosis: Identity, Mechanisms and Potential Triggers. Front Immunol. 2020 May;11:760. doi: 10.3389/fimmu.2020.00760Jog NR, McClain MT, Heinlen LD, et al. Epstein Barr virus nuclear antigen 1 (EBNA-1) peptides recognized by adult multiple sclerosis patient sera induce neurologic symptoms in a murine model. J Autoimmun. 2020 Jan;106:102332. doi: 10.1016/j.jaut.2019.102332Jog NR, McClain MT, Heinlen LD, et al. Epstein Barr virus nuclear antigen 1 (EBNA-1) peptides recognized by adult multiple sclerosis patient sera induce neurologic symptoms in a murine model. J Autoimmun. 2020 Jan;106:102332. doi: 10.1016/j.jaut.2019.102332Liu R, Du S, Zhao L, et al. Autoreactive lymphocytes in multiple sclerosis: Pathogenesis and treatment target. Front Immunol. 2022 Sep;13:996469. doi: 10.3389/fimmu.2022.996469Liu R, Du S, Zhao L, et al. Autoreactive lymphocytes in multiple sclerosis: Pathogenesis and treatment target. Front Immunol. 2022 Sep;13:996469. doi: 10.3389/fimmu.2022.996469Absinta M, Maric D, Gharagozloo M, et al. A lymphocyte-microglia-astrocyte axis in chronic active multiple sclerosis. Nature. 2021 Sep;597(7878):709-14. doi: 10.1038/s41586-021-03892-7Absinta M, Maric D, Gharagozloo M, et al. A lymphocyte-microglia-astrocyte axis in chronic active multiple sclerosis. Nature. 2021 Sep;597(7878):709-14. doi: 10.1038/s41586-021-03892-7Ten Bosch GJA, Bolk J, 't Hart BA, Laman JD. Multiple sclerosis is linked to MAPKERK overactivity in microglia. Mol Med (Berl). 2021 Aug;99(8):1033-42. doi: 10.1007/s00109-021-02080-4Ten Bosch GJA, Bolk J, 't Hart BA, Laman JD. Multiple sclerosis is linked to MAPKERK overactivity in microglia. Mol Med (Berl). 2021 Aug;99(8):1033-42. doi: 10.1007/s00109-021-02080-4Kumar N, Sharma N, Mehan S. Connection between JAK/STAT and PPARγ Signaling During the Progression of Multiple Sclerosis: Insights into the Modulation of T-Cells and Immune Responses in the Brain. Curr Mol Pharmacol. 2021;14(5):823-37. doi: 10.2174/1874467214666210301121432Kumar N, Sharma N, Mehan S. Connection between JAK/STAT and PPARγ Signaling During the Progression of Multiple Sclerosis: Insights into the Modulation of T-Cells and Immune Responses in the Brain. Curr Mol Pharmacol. 2021;14(5):823-37. doi: 10.2174/1874467214666210301121432Massey J, Jackson K, Singh M, et al. Haematopoietic Stem Cell Transplantation Results in Extensive Remodelling of the Clonal T Cell Repertoire in Multiple Sclerosis. Front Immunol. 2022 Feb;13:798300. doi: 10.3389/fimmu.2022.798300Massey J, Jackson K, Singh M, et al. Haematopoietic Stem Cell Transplantation Results in Extensive Remodelling of the Clonal T Cell Repertoire in Multiple Sclerosis. Front Immunol. 2022 Feb;13:798300. doi: 10.3389/fimmu.2022.798300Reynaud JM, Jegou JF, Welsch JC, Horvat B. Human herpesvirus 6A infection in CD46 transgenic mice: viral persistence in the brain and increased production of proinflammatory chemokines via Toll-like receptor 9. J Virol. 2014 May;88(10):5421-36. doi: 10.1128/JVI.03763-13Reynaud JM, Jegou JF, Welsch JC, Horvat B. Human herpesvirus 6A infection in CD46 transgenic mice: viral persistence in the brain and increased production of proinflammatory chemokines via Toll-like receptor 9. J Virol. 2014 May;88(10):5421-36. doi: 10.1128/JVI.03763-13Leibovitch E, Wohler JE, Cummings Macri SM, et al. Novel marmoset (Callithrix jacchus) model of human Herpesvirus 6A and 6B infections: immunologic, virologic and radiologic characterization. PLoS Pathog. 2013 Jan;9(1):e1003138. doi: 10.1371/journal.ppat.1003138Leibovitch E, Wohler JE, Cummings Macri SM, et al. Novel marmoset (Callithrix jacchus) model of human Herpesvirus 6A and 6B infections: immunologic, virologic and radiologic characterization. PLoS Pathog. 2013 Jan;9(1):e1003138. doi: 10.1371/journal.ppat.1003138Challoner PB, Smith KT, Parker JD, et al. Plaque-associated expression of human herpesvirus 6 in multiple sclerosis. Proc Natl Acad Sci U S A. 1995 Aug;92(16):7440-4. doi: 10.1073/pnas.92.16.7440Challoner PB, Smith KT, Parker JD, et al. Plaque-associated expression of human herpesvirus 6 in multiple sclerosis. Proc Natl Acad Sci U S A. 1995 Aug;92(16):7440-4. doi: 10.1073/pnas.92.16.7440Chapenko S, Millers A, Nora Z, et al. Correlation between HHV-6 reactivation and multiple sclerosis disease activity. J Med Virol. 2003 Jan;69(1):111-7. doi: 10.1002/jmv.10258Chapenko S, Millers A, Nora Z, et al. Correlation between HHV-6 reactivation and multiple sclerosis disease activity. J Med Virol. 2003 Jan;69(1):111-7. doi: 10.1002/jmv.10258Soldan SS, Fogdell-Hahn A, Brennan MB, et al. Elevated serum and cerebrospinal fluid levels of soluble human herpesvirus type 6 cellular receptor, membrane cofactor protein, in patients with multiple sclerosis. Ann Neurol. 2001 Oct;50(4):486-93. doi: 10.1002/ana.1135Soldan SS, Fogdell-Hahn A, Brennan MB, et al. Elevated serum and cerebrospinal fluid levels of soluble human herpesvirus type 6 cellular receptor, membrane cofactor protein, in patients with multiple sclerosis. Ann Neurol. 2001 Oct;50(4):486-93. doi: 10.1002/ana.1135Zheng W, Xu Q, Zhang Y, et al. Toll-like receptor-mediated innate immunity against herpesviridae infection: a current perspective on viral infection signaling pathways. J Virol. 2020 Dec;17(1):192. doi: 10.1186/s12985-020-01463-2Zheng W, Xu Q, Zhang Y, et al. Toll-like receptor-mediated innate immunity against herpesviridae infection: a current perspective on viral infection signaling pathways. J Virol. 2020 Dec;17(1):192. doi: 10.1186/s12985-020-01463-2Mori Y, Yang X, Akkapaiboon P, et al. Human herpesvirus 6 variant A glycoprotein H-glycoprotein L-glycoprotein Q complex associates with human CD46. J Virol. 2003 Apr;77(8):4992-9. doi: 10.1128/jvi.77.8.4992-4999.2003Mori Y, Yang X, Akkapaiboon P, et al. Human herpesvirus 6 variant A glycoprotein H-glycoprotein L-glycoprotein Q complex associates with human CD46. J Virol. 2003 Apr;77(8):4992-9. doi: 10.1128/jvi.77.8.4992-4999.2003Engdahl E, Gustafsson R, Huang J, et al. Increased Serological Response Against Human Herpesvirus 6A Is Associated With Risk for Multiple Sclerosis. Front Immunol. 2019 Nov;10:2715. doi: 10.3389/fimmu.2019.02715Engdahl E, Gustafsson R, Huang J, et al. Increased Serological Response Against Human Herpesvirus 6A Is Associated With Risk for Multiple Sclerosis. Front Immunol. 2019 Nov;10:2715. doi: 10.3389/fimmu.2019.02715De Bolle L, Van Loon J, De Clercq E, Naesens L. Quantitative analysis of human herpesvirus 6 cell tropism. J Med Virol. 2005 Jan;75(1):76-85. doi: 10.1002/jmv.20240De Bolle L, Van Loon J, De Clercq E, Naesens L. Quantitative analysis of human herpesvirus 6 cell tropism. J Med Virol. 2005 Jan;75(1):76-85. doi: 10.1002/jmv.20240Goodman AD, Mock DJ, Powers JM, et al. Human herpesvirus 6 genome and antigen in acute multiple sclerosis lesions. Infect Dis. 2003 May;187(9):1365-76. doi: 10.1086/368172Goodman AD, Mock DJ, Powers JM, et al. Human herpesvirus 6 genome and antigen in acute multiple sclerosis lesions. Infect Dis. 2003 May;187(9):1365-76. doi: 10.1086/368172Ortega-Madueno I, Garcia-Montojo M, Dominguez-Mozo MI, et al. Anti-human herpesvirus 6A/B IgG correlates with relapses and progression in multiple sclerosis. PLoS One. 2014 Aug;9(8):e104836. doi: 10.1371/journal.pone.0104836Ortega-Madueno I, Garcia-Montojo M, Dominguez-Mozo MI, et al. Anti-human herpesvirus 6A/B IgG correlates with relapses and progression in multiple sclerosis. PLoS One. 2014 Aug;9(8):e104836. doi: 10.1371/journal.pone.0104836Amini R, Karampoor S, Zahednasab H, et al. Serum levels of matrix metalloproteinase-2, -9, and vitamin D in patients with multiple sclerosis with or without herpesvirus-6 seropositivity. Braz Infect Dis. 2020 Mar-Apr;;24(2):144-9. doi: 10.1016/j.bjid.2020.02.001Amini R, Karampoor S, Zahednasab H, et al. Serum levels of matrix metalloproteinase-2, -9, and vitamin D in patients with multiple sclerosis with or without herpesvirus-6 seropositivity. Braz Infect Dis. 2020 Mar-Apr;;24(2):144-9. doi: 10.1016/j.bjid.2020.02.001Tejada-Simon MV, Zang YC, Hong J, et al. Cross-reactivity with myelin basic protein and human herpesvirus-6 in multiple sclerosis. Ann Neurol. 2003 Feb;53(2):189-97. doi: 10.1002/ana.10425Tejada-Simon MV, Zang YC, Hong J, et al. Cross-reactivity with myelin basic protein and human herpesvirus-6 in multiple sclerosis. Ann Neurol. 2003 Feb;53(2):189-97. doi: 10.1002/ana.10425Pi KS, Bortolotti D, Sang Y, et al. Studying the Interactions of U24 from HHV-6 in Order to Further Elucidate Its Potential Role in MS. Viruses. 2022 Oct;14(11):2384. doi: 10.3390/v14112384Pi KS, Bortolotti D, Sang Y, et al. Studying the Interactions of U24 from HHV-6 in Order to Further Elucidate Its Potential Role in MS. Viruses. 2022 Oct;14(11):2384. doi: 10.3390/v14112384Biström M, Jons D, Engdahl E, et al. Epstein-Barr virus infection after adolescence and human herpesvirus 6A as risk factors for multiple sclerosis. Eur Neurol. 2021 Feb;28(2):579-86. doi: 10.1111/ene.14597Biström M, Jons D, Engdahl E, et al. Epstein-Barr virus infection after adolescence and human herpesvirus 6A as risk factors for multiple sclerosis. Eur Neurol. 2021 Feb;28(2):579-86. doi: 10.1111/ene.14597Maple 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 Mar;80(3):320-5. doi: 10.1016/j.jinf.2019.10.017Maple 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 Mar;80(3):320-5. doi: 10.1016/j.jinf.2019.10.017Langer-Gould A, Wu J, Lucas R, et al. Epstein–Barr virus, cytomegalovirus, and multiple sclerosis susceptibility: A multiethnic study. Neurology. 2017 Sep;89(13):1330-7. doi: 10.1212/WNL.0000000000004412Langer-Gould A, Wu J, Lucas R, et al. Epstein–Barr virus, cytomegalovirus, and multiple sclerosis susceptibility: A multiethnic study. Neurology. 2017 Sep;89(13):1330-7. doi: 10.1212/WNL.0000000000004412Grut V, Biström M, Salzer J, et al. Cytomegalovirus seropositivity is associated with reduced risk of multiple sclerosis-a presymptomatic case-control study. Eur Neurol. 2021 Sep;28(9):3072-9. doi: 10.1111/ene.14961Grut V, Biström M, Salzer J, et al. Cytomegalovirus seropositivity is associated with reduced risk of multiple sclerosis-a presymptomatic case-control study. Eur Neurol. 2021 Sep;28(9):3072-9. doi: 10.1111/ene.14961Perez-Perez S, Dominguez-Mozo MI, Garcia-Martinez MA, et al. Anti-Human Herpesvirus 6 A/B Antibodies Titers Correlate With Multiple Sclerosis-Associated Retrovirus Envelope Expression. Front Immunol. 2021 Nov;12:798003. doi: 10.3389/fimmu.2021.798003Perez-Perez S, Dominguez-Mozo MI, Garcia-Martinez MA, et al. Anti-Human Herpesvirus 6 A/B Antibodies Titers Correlate With Multiple Sclerosis-Associated Retrovirus Envelope Expression. Front Immunol. 2021 Nov;12:798003. doi: 10.3389/fimmu.2021.798003Schmidt H, Williamson D, Ashley-Koch A. HLA-DR15 haplotype and multiple sclerosis: a HuGE review. Am J Epidemiol. 2007 May;165(10):1097-109. doi: 10.1093/aje/kwk118Schmidt H, Williamson D, Ashley-Koch A. HLA-DR15 haplotype and multiple sclerosis: a HuGE review. Am J Epidemiol. 2007 May;165(10):1097-109. doi: 10.1093/aje/kwk118De Jager PL, Chibnik LB, Cui J, et al. Integration of genetic risk factors into a clinical algorithm for multiple sclerosis susceptibility: a weighted genetic risk score. Lancet Neurol. 2009 Dec;8(12):1111-9. doi: 10.1016/S1474-4422(09)70275-3De Jager PL, Chibnik LB, Cui J, et al. Integration of genetic risk factors into a clinical algorithm for multiple sclerosis susceptibility: a weighted genetic risk score. Lancet Neurol. 2009 Dec;8(12):1111-9. doi: 10.1016/S1474-4422(09)70275-3Ramroodi N, Sanadgol N, Ganjali Z, et al. Monitoring of active human herpes virus 6 infection in Iranian patients with different subtypes of multiple sclerosis. J Pathog. 2013 Jan;2013:194932. doi: 10.1155/2013/194932Ramroodi N, Sanadgol N, Ganjali Z, et al. Monitoring of active human herpes virus 6 infection in Iranian patients with different subtypes of multiple sclerosis. J Pathog. 2013 Jan;2013:194932. doi: 10.1155/2013/194932Mora JR, Iwata M, von Andrian UH. Vitamin effects on the immune system: vitamins A and D take centre stage. Nat Rev Immunol. 2008 Sep;8(9):685-98. doi: 10.1038/nri2378Mora JR, Iwata M, von Andrian UH. Vitamin effects on the immune system: vitamins A and D take centre stage. Nat Rev Immunol. 2008 Sep;8(9):685-98. doi: 10.1038/nri2378Simpson S Jr, Wang W, Otahal P, et al. Latitude continues to be significantly associated with the prevalence of multiple sclerosis: an updated meta-analysis. Neurol Neurosurg Psychiatry. 2019 Nov;90(11):1193-200. doi: 10.1136/jnnp-2018-320189Simpson S Jr, Wang W, Otahal P, et al. Latitude continues to be significantly associated with the prevalence of multiple sclerosis: an updated meta-analysis. Neurol Neurosurg Psychiatry. 2019 Nov;90(11):1193-200. doi: 10.1136/jnnp-2018-320189Lau LW, Cua R, Keough MB, et al. Pathophysiology of the brain extracellular matrix: a new target for remyelination. Nat Rev Neurosci. 2013 Oct;14(10):722-9. doi: 10.1038/nrn3550Lau LW, Cua R, Keough MB, et al. Pathophysiology of the brain extracellular matrix: a new target for remyelination. Nat Rev Neurosci. 2013 Oct;14(10):722-9. doi: 10.1038/nrn3550Leppert D, Ford J, Stabler G, et al. Matrix metalloproteinase-9 (gelatinase B) is selectively elevated in CSF during relapses and stable phases of multiple sclerosis. Brain. 1998 Dec;121 (Pt 12):2327-34. doi: 10.1093/brain/121.12.2327Leppert D, Ford J, Stabler G, et al. Matrix metalloproteinase-9 (gelatinase B) is selectively elevated in CSF during relapses and stable phases of multiple sclerosis. Brain. 1998 Dec;121 (Pt 12):2327-34. doi: 10.1093/brain/121.12.2327Bjornevik K, Munger KL, Cortese M, et al. Serum Neurofilament Light Chain Levels in Patients With Presymptomatic Multiple Sclerosis. JAMA Neurol. 2020 Jan;77(1):58-64. doi: 10.1001/jamaneurol.2019.3238Bjornevik K, Munger KL, Cortese M, et al. Serum Neurofilament Light Chain Levels in Patients With Presymptomatic Multiple Sclerosis. JAMA Neurol. 2020 Jan;77(1):58-64. doi: 10.1001/jamaneurol.2019.3238Gaetani L, Parnetti L, Calabresi P, Di Filippo M. Tracing Neurological Diseases in the Presymptomatic Phase: Insights From Neurofilament Light Chain. Front Neurosci. 2021 May;15:672954. doi: 10.3389/fnins.2021.672954Gaetani L, Parnetti L, Calabresi P, Di Filippo M. Tracing Neurological Diseases in the Presymptomatic Phase: Insights From Neurofilament Light Chain. Front Neurosci. 2021 May;15:672954. doi: 10.3389/fnins.2021.672954Kuhle J, Plavina T, Barro C, et al. Neurofilament light levels are associated with long-term outcomes in multiple sclerosis. Mult Scler. 2020 Nov;26(13):1691-9. doi: 10.1177/1352458519885613Kuhle J, Plavina T, Barro C, et al. Neurofilament light levels are associated with long-term outcomes in multiple sclerosis. Mult Scler. 2020 Nov;26(13):1691-9. doi: 10.1177/1352458519885613Ziemssen T, Arnold DL, Alvarez E, et al. Prognostic Value of Serum Neurofilament Light Chain for Disease Activity and Worsening in Patients With Relapsing Multiple Sclerosis: Results From the Phase 3 ASCLEPIOS I and II Trials. Front Immunol. 2022 Mar;13:852563. doi: 10.3389/fimmu.2022.852563Ziemssen T, Arnold DL, Alvarez E, et al. Prognostic Value of Serum Neurofilament Light Chain for Disease Activity and Worsening in Patients With Relapsing Multiple Sclerosis: Results From the Phase 3 ASCLEPIOS I and II Trials. Front Immunol. 2022 Mar;13:852563. doi: 10.3389/fimmu.2022.852563Grut V, Biström M, Salzer J, et al. Human herpesvirus 6A and axonal injury before the clinical onset of multiple sclerosis. Brain. 2024 Jan;147(1):177-85. doi: 10.1093/brain/awad374Grut V, Biström M, Salzer J, et al. Human herpesvirus 6A and axonal injury before the clinical onset of multiple sclerosis. Brain. 2024 Jan;147(1):177-85. doi: 10.1093/brain/awad374Lünemann JD, Sao Aviles A, Tintore M, et al. Cytomegalovirus immune responses are associated with lower serum NfL and disability accumulation risk at multiple sclerosis onset. Mult Scler. 2024 Oct;30(11-12):1445-54. doi: 10.1177/13524585241274571Lünemann JD, Sao Aviles A, Tintore M, et al. Cytomegalovirus immune responses are associated with lower serum NfL and disability accumulation risk at multiple sclerosis onset. Mult Scler. 2024 Oct;30(11-12):1445-54. doi: 10.1177/13524585241274571

The authors declare that there are no conflicts of interest present.