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Published in: BMC Neurology 1/2022

Open Access 01-12-2022 | Herpes Virus | Research

Human herpesvirus 6 infection as a trigger of multiple sclerosis: an update of recent literature

Authors: K. I. Voumvourakis, P.C. Fragkou, D. K. Kitsos, K. Foska, M. Chondrogianni, S. Tsiodras

Published in: BMC Neurology | Issue 1/2022

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Abstract

Background

This is an update on the existing evidence regarding a relationship between infection with human herpesvirus 6 (HHV-6) and multiple sclerosis (MS) in order to contribute on the attempt to define the nature and strength of that relationship.

Results

Study quality was assessed using the criteria proposed by Moore and Wolfson and by the classification criteria used by the Canadian Task Force on the Periodic Health Examination. Studies were categorized both by experimental technique and by quality (high [A], intermediate [B], and low [C]) as determined by the Moore and Wolfson criteria. Overall, 27 (90%) of 30 studies, 18 (86%) of which were classified as A quality, reached a statistically significant result. According to the Canadian Task Force classification, all studies were categorized as evidence of qualityII-1. Limitations of the available experimental techniques and perspectives for future research are discussed.

Conclusions

The current review continues to emphasize the need for further, objective, evidence-based examination of the relationship between HHV-6 infection and multiple sclerosis.
Literature
1.
2.
go back to reference Panitch HS. Influence of infection on exacerbations of multiple sclerosis. Ann Neurol. 1994;36(suppl):S25–8.CrossRef Panitch HS. Influence of infection on exacerbations of multiple sclerosis. Ann Neurol. 1994;36(suppl):S25–8.CrossRef
3.
go back to reference Sibley WA, Bamford CR, Clark K. Clinical viral infections and multiple sclerosis. Lancet. 1985;1(8441):1313–5.CrossRef Sibley WA, Bamford CR, Clark K. Clinical viral infections and multiple sclerosis. Lancet. 1985;1(8441):1313–5.CrossRef
5.
go back to reference Moore FG, Wolfson C. Human herpes virus 6 and multiple sclerosis. Acta Neurol Scand. 2002;106(2):63–83.CrossRef Moore FG, Wolfson C. Human herpes virus 6 and multiple sclerosis. Acta Neurol Scand. 2002;106(2):63–83.CrossRef
6.
go back to reference Canadian Task Force on the Periodic Health Examination. The periodic health examination. Can Med Assoc J. 1979;121(9):1193–254. Canadian Task Force on the Periodic Health Examination. The periodic health examination. Can Med Assoc J. 1979;121(9):1193–254.
7.
go back to reference Ortega-Madueño 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;9(8):e104836 Published 2014 Aug 11.CrossRef Ortega-Madueño 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;9(8):e104836 Published 2014 Aug 11.CrossRef
8.
go back to reference Stüve O, Marra CM, Jerome KR, Selter RC, Biberacher V, Grummel V, et al. Immune surveillance in multiple sclerosis patients treated with natalizumab. Ann Neurol. 2006;59:743–7.CrossRef Stüve O, Marra CM, Jerome KR, Selter RC, Biberacher V, Grummel V, et al. Immune surveillance in multiple sclerosis patients treated with natalizumab. Ann Neurol. 2006;59:743–7.CrossRef
9.
go back to reference Selter RC, Biberacher V, Grummel V, et al. Natalizumab treatment decreases serum IgM and IgG levels in multiple sclerosis patients. MultScler. 2013;19:1454–61. Selter RC, Biberacher V, Grummel V, et al. Natalizumab treatment decreases serum IgM and IgG levels in multiple sclerosis patients. MultScler. 2013;19:1454–61.
10.
go back to reference Warnke C, Stettner M, Lehmensiek V, et al. Natalizumab exerts a suppressive effect on surrogates of B cell function in blood and CSF. MultScler. 2015;21:1036–44. Warnke C, Stettner M, Lehmensiek V, et al. Natalizumab exerts a suppressive effect on surrogates of B cell function in blood and CSF. MultScler. 2015;21:1036–44.
11.
go back to reference Ben-Fredj N, Ben-Selma W, Rotola A, et al. Prevalence of human herpesvirus U94/REP antibodies and DNA in Tunisian multiple sclerosis patients. J Neurovirol. 2013;19(1):42–7.CrossRef Ben-Fredj N, Ben-Selma W, Rotola A, et al. Prevalence of human herpesvirus U94/REP antibodies and DNA in Tunisian multiple sclerosis patients. J Neurovirol. 2013;19(1):42–7.CrossRef
12.
go back to reference Simpson S Jr, Taylor B, Dwyer DE, et al. Anti-HHV-6 IgG titer significantly predicts subsequent relapse risk in multiple sclerosis. MultScler. 2012;18(6):799–806. Simpson S Jr, Taylor B, Dwyer DE, et al. Anti-HHV-6 IgG titer significantly predicts subsequent relapse risk in multiple sclerosis. MultScler. 2012;18(6):799–806.
14.
go back to reference Khaki M, Ghazavi A, Ghasami K, et al. Evaluation of viral antibodies in Iranian multiple sclerosis patients. Neurosciences (Riyadh). 2011;16(3):224–8. Khaki M, Ghazavi A, Ghasami K, et al. Evaluation of viral antibodies in Iranian multiple sclerosis patients. Neurosciences (Riyadh). 2011;16(3):224–8.
15.
go back to reference Behzad-Behbahani A, Mikaeili MH, Entezam M, et al. Human herpesvirus-6 viral load and antibody titer in serum samples of patients with multiple sclerosis. J Microbiol Immunol Infect. 2011;44(4):247–51.CrossRef Behzad-Behbahani A, Mikaeili MH, Entezam M, et al. Human herpesvirus-6 viral load and antibody titer in serum samples of patients with multiple sclerosis. J Microbiol Immunol Infect. 2011;44(4):247–51.CrossRef
17.
go back to reference Biström M, Jons D, Engdahl E, et al. Epstein-Barr virus infection after adolescence and human herpesvirus 6A as risk factors for multiple sclerosis. Eur J Neurol. 2021;28(2):579–86.CrossRef Biström M, Jons D, Engdahl E, et al. Epstein-Barr virus infection after adolescence and human herpesvirus 6A as risk factors for multiple sclerosis. Eur J Neurol. 2021;28(2):579–86.CrossRef
18.
go back to reference Amini R, Karampoor S, Zahednasab H, Keyvani 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 J Infect Dis. 2020;24(2):144–9.CrossRef Amini R, Karampoor S, Zahednasab H, Keyvani 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 J Infect Dis. 2020;24(2):144–9.CrossRef
19.
go back to reference Ahmadi JalaliMoghadam M, Honarmand H. Human Herpesvirus 6 Viremia in Patients with Classic Multiple Scelerosis in Guilan, Iran. JoMMID. 2014;2(4):133–7. Ahmadi JalaliMoghadam M, Honarmand H. Human Herpesvirus 6 Viremia in Patients with Classic Multiple Scelerosis in Guilan, Iran. JoMMID. 2014;2(4):133–7.
21.
go back to reference Garcia-Montojo M, De Las HV, Dominguez-Mozo M, et al. Human herpesvirus 6 and effectiveness of interferon β1b in multiple sclerosis patients. Eur J Neurol. 2011;18(8):1027–35.CrossRef Garcia-Montojo M, De Las HV, Dominguez-Mozo M, et al. Human herpesvirus 6 and effectiveness of interferon β1b in multiple sclerosis patients. Eur J Neurol. 2011;18(8):1027–35.CrossRef
22.
go back to reference Esmaili K, Amini K. Detection of Human Herpes Virus Type 6 and Varicella Zoster Virus in the Urine of Patients with Multiple Sclerosis in Kerman Province. Iran Shefaye Khatam. 2018;6(3):19–24.CrossRef Esmaili K, Amini K. Detection of Human Herpes Virus Type 6 and Varicella Zoster Virus in the Urine of Patients with Multiple Sclerosis in Kerman Province. Iran Shefaye Khatam. 2018;6(3):19–24.CrossRef
24.
go back to reference Dominguez-Mozo MI, Garcia-Montojo M, De Las Heras V, et al. MHC2TA mRNA levels and human herpesvirus 6 in multiple sclerosis patients treated with interferon beta along two-year follow-up. BMC Neurol. 2012;12:107 Published 2012 Sep 25.CrossRef Dominguez-Mozo MI, Garcia-Montojo M, De Las Heras V, et al. MHC2TA mRNA levels and human herpesvirus 6 in multiple sclerosis patients treated with interferon beta along two-year follow-up. BMC Neurol. 2012;12:107 Published 2012 Sep 25.CrossRef
25.
go back to reference Garcia-Montojo M, Martinez A, De Las HV, et al. Herpesvirus active replication in multiple sclerosis: a genetic control? J Neurol Sci. 2011;311(1–2):98–102.CrossRef Garcia-Montojo M, Martinez A, De Las HV, et al. Herpesvirus active replication in multiple sclerosis: a genetic control? J Neurol Sci. 2011;311(1–2):98–102.CrossRef
26.
go back to reference Vandenbroeck K, Alloza I, Swaminathan B, et al. Validation of IRF5 as multiple sclerosis risk gene: putative role in interferon beta therapy and human herpes virus-6 infection. Genes Immun. 2011;12:40–5.CrossRef Vandenbroeck K, Alloza I, Swaminathan B, et al. Validation of IRF5 as multiple sclerosis risk gene: putative role in interferon beta therapy and human herpes virus-6 infection. Genes Immun. 2011;12:40–5.CrossRef
27.
go back to reference Alvarez-Lafuente R, Martinez A, Garcia-Montojo M, et al. MHC2TA rs4774C and HHV-6A active replication in multiple sclerosis patients. Eur J Neurol. 2010;17:129–35.CrossRef Alvarez-Lafuente R, Martinez A, Garcia-Montojo M, et al. MHC2TA rs4774C and HHV-6A active replication in multiple sclerosis patients. Eur J Neurol. 2010;17:129–35.CrossRef
29.
go back to reference Latham L.B., Lee M.J., LincolnJ A, et al. Antivirus immune activity in multiple sclerosis correlates with MRI activity. Acta NeurolScand. 2016;133:17–24.CrossRef Latham L.B., Lee M.J., LincolnJ A, et al. Antivirus immune activity in multiple sclerosis correlates with MRI activity. Acta NeurolScand. 2016;133:17–24.CrossRef
30.
go back to reference Ferrante P, Mancuso R, Pagani E, et al. Molecular evidences for a role of HSV-1 in multiple sclerosis clinical acute attack. J Neurovirol. 2000;6(Suppl 2):S109–14.PubMed Ferrante P, Mancuso R, Pagani E, et al. Molecular evidences for a role of HSV-1 in multiple sclerosis clinical acute attack. J Neurovirol. 2000;6(Suppl 2):S109–14.PubMed
31.
go back to reference Domínguez-Mozo MI, Nieto-Guerrero A, Pérez-Pérez S, García-Martínez MÁ, Arroyo R, Álvarez-Lafuente R. MicroRNAs of Human Herpesvirus 6A and 6B in Serum and Cerebrospinal Fluid of Multiple Sclerosis Patients. Front Immunol. 2020;18(11):2142.CrossRef Domínguez-Mozo MI, Nieto-Guerrero A, Pérez-Pérez S, García-Martínez MÁ, Arroyo R, Álvarez-Lafuente R. MicroRNAs of Human Herpesvirus 6A and 6B in Serum and Cerebrospinal Fluid of Multiple Sclerosis Patients. Front Immunol. 2020;18(11):2142.CrossRef
32.
go back to reference Alenda R, Álvarez-Lafuente R, Costa-Frossard L, et al. Identification of the major HHV-6 antigen recognized by cerebrospinal fluid IgG in multiple sclerosis. Eur J Neurol. 2014;21(8):1096–101.CrossRef Alenda R, Álvarez-Lafuente R, Costa-Frossard L, et al. Identification of the major HHV-6 antigen recognized by cerebrospinal fluid IgG in multiple sclerosis. Eur J Neurol. 2014;21(8):1096–101.CrossRef
33.
go back to reference Pietiläinen-Nicklén J, Virtanen JO, Uotila L, et al. HHV-6-positivity in diseases with demyelination. J Clin Virol. 2014;61(2):216–9.CrossRef Pietiläinen-Nicklén J, Virtanen JO, Uotila L, et al. HHV-6-positivity in diseases with demyelination. J Clin Virol. 2014;61(2):216–9.CrossRef
34.
go back to reference Pietiläinen J, Virtanen JO, Uotila L, et al. HHV-6 infection in multiple sclerosis. A clinical and laboratory analysis. Eur J Neurol. 2010;17:506–9.CrossRef Pietiläinen J, Virtanen JO, Uotila L, et al. HHV-6 infection in multiple sclerosis. A clinical and laboratory analysis. Eur J Neurol. 2010;17:506–9.CrossRef
35.
go back to reference Virtanen JO, Wohler J, Fenton K, et al. Oligoclonal bands in multiple sclerosis reactive against two herpesviruses and association with magnetic resonance imaging findings. MultScler. 2014;20(1):27–34. Virtanen JO, Wohler J, Fenton K, et al. Oligoclonal bands in multiple sclerosis reactive against two herpesviruses and association with magnetic resonance imaging findings. MultScler. 2014;20(1):27–34.
36.
go back to reference Virtanen JO, Pietiläinen-Nicklén J, Uotila L, et al. Intrathecal human herpesvirus 6 antibodies in multiple sclerosis and other demyelinating diseases presenting as oligoclonal bands in cerebrospinal fluid. J Neuroimmunol. 2011;237(1–2):93–7.CrossRef Virtanen JO, Pietiläinen-Nicklén J, Uotila L, et al. Intrathecal human herpesvirus 6 antibodies in multiple sclerosis and other demyelinating diseases presenting as oligoclonal bands in cerebrospinal fluid. J Neuroimmunol. 2011;237(1–2):93–7.CrossRef
37.
go back to reference Perlejewski K, Bukowska-Ośko I, Rydzanicz M, et al. Search for viral agents in cerebrospinal fluid in patients with multiple sclerosis using real-time PCR and metagenomics. PLoS One. 2020;15(10):e0240601.CrossRef Perlejewski K, Bukowska-Ośko I, Rydzanicz M, et al. Search for viral agents in cerebrospinal fluid in patients with multiple sclerosis using real-time PCR and metagenomics. PLoS One. 2020;15(10):e0240601.CrossRef
38.
go back to reference Panitch HS. Influence of infection on exacerbations of multiple sclerosis. Ann Neurol. 1994;36(suppl):S25–8.CrossRef Panitch HS. Influence of infection on exacerbations of multiple sclerosis. Ann Neurol. 1994;36(suppl):S25–8.CrossRef
39.
go back to reference Leibovitch EC, Jacobson S. Evidence linking HHV-6 with multiple sclerosis: an update. CurrOpinVirol. 2014;9:127–33. Leibovitch EC, Jacobson S. Evidence linking HHV-6 with multiple sclerosis: an update. CurrOpinVirol. 2014;9:127–33.
Metadata
Title
Human herpesvirus 6 infection as a trigger of multiple sclerosis: an update of recent literature
Authors
K. I. Voumvourakis
P.C. Fragkou
D. K. Kitsos
K. Foska
M. Chondrogianni
S. Tsiodras
Publication date
01-12-2022
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2022
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-022-02568-7

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