Human herpesvirus 6 infection as a trigger of multiple sclerosis

Mayo Clinic Proceedings

Volumn 85, Issue 11, 2010, Pages 1023-1030

  Voumvourakis, Konstantine I ^a   Kitsos, Dimitrios K ^a   Tsiodras, Sotirios ^a   Petrikkos, George ^a   Stamboulis, Eleftherios ^a  

^a NATIONAL AND KAPODISTRIAN UNIVERSITY OF ATHENS   (Greece)

Author keywords

[No Author keywords available]

Indexed keywords

IMMUNOGLOBULIN G ANTIBODY; IMMUNOGLOBULIN M ANTIBODY; VIRUS DNA;

ANTIBODY BLOOD LEVEL; CEREBROSPINAL FLUID LEVEL; DISEASE ASSOCIATION; HERPES VIRUS INFECTION; HUMAN; HUMAN HERPESVIRUS 6; IMMUNOHISTOCHEMISTRY; MULTIPLE SCLEROSIS; NEUROPATHOLOGY; PERIPHERAL BLOOD MONONUCLEAR CELL; POLYMERASE CHAIN REACTION; REVIEW; SEROLOGY; VIRUS DETECTION;

EID: 78149332048     PISSN: 00256196     EISSN: None     Source Type: Journal    
DOI: 10.4065/mcp.2010.0350     Document Type: Review

References (80)

1. Compston A, Coles A. Multiple sclerosis. Lancet. 2008;372(9648):1502- 1517.
2. Gilden DH. Infectious causes of multiple sclerosis. Lancet Neurol. 2005;4(3):195-202.
3. Filippi M, Bozzali M, Rovaris M, et al. Evidence for widespread axonal damage at the earliest clinical stage of multiple sclerosis. Brain. 2003;126(pt 2):433-437.
4. Babbe H, Roers A, Waisman A, et al. Clonal expansions of CD8(+) T cells dominate the T cell infiltrate in active multiple sclerosis lesions as shown by micromanipulation and single cell polymerase chain reaction. J Exp Med. 2000;192(3):393-404.
5. Kapeller P, McLean MA, Griffin CM, et al. Preliminary evidence for neuronal damage in cortical grey matter and normal appearing white matter in short duration relapsing-remitting multiple sclerosis: a quantitative MR spectroscopic imaging study. J Neurol. 2001;248(2):131-138.
6. Edwards S, Zvartau M, Clarke H, Irving W, Blumhardt LD. Clinical relapses and disease activity on magnetic resonance imaging associated with viral upper respiratory tract infections in multiple sclerosis. J Neurol Neurosurg Psychiatry. 1998;64(6):736-741. (Pubitemid 28274406)
7. Panitch HS. Influence of infection on exacerbations of multiple sclerosis. Ann Neurol. 1994;36(suppl):S25-S28.
8. Sibley WA, Bamford CR, Clark K. Clinical viral infections and multiple sclerosis. Lancet. 1985;1(8441):1313-1315.
9. Dockrell DH, Smith TF, Paya CV. Human herpesvirus 6. Mayo Clin Proc. 1999;74(2):163-170.
10. Meinl E. Concepts of viral pathogenesis of multiple sclerosis. Curr Opin Neurol. 1999;12(3):303-307.
11. Moore FG, Wolfson C. Human herpes virus 6 and multiple sclerosis. Acta Neurol Scand. 2002;106(2):63-83. (Pubitemid 34831922)
12. Canadian Task Force on the Periodic Health Examination. The periodic health examination. Can Med Assoc J. 1979;121(9):1193-1254.
13. Kuusisto H, Hyoty H, Kares S, Kinnunen E, Elovaara I. Human herpes virus 6 and multiple sclerosis: a Finnish twin study. Mult Scler. 2008;14(1):54-58.
14. Virtanen JO, Farkkila M, Multanen J, et al. Evidence for human herpesvirus 6 variant A antibodies in multiple sclerosis: diagnostic and therapeutic implications. J Neurovirol. 2007;13(4):347-352.
15. Derfuss T, Hohlfeld R, Meinl E. Intrathecal antibody (IgG) production against human herpesvirus type 6 occurs in about 20% of multiple sclerosis patients and might be linked to a polyspcific B-cell response. J Neurol. 2005;252(8):968-971.
16. Villoslada P, Juste C, Tintore M, et al. The immune response against herpesvirus is more prominent in the early stages of MS. Neurology. 2003;60(12):1944-1948.
17. Chapenko S, Millers A, Nora Z, Logina I, Kukaine R, Murovska M. Correlation between HHV-6 reactivation and multiple sclerosis disease activity. J Med Virol. 2003;69(1):111-117.
18. Gutierrez J, Vergara MJ, Guerrero M, et al. Multiple sclerosis and human herpesvirus 6. Infection. 2002;30(3):145-149.
19. Xu Y, Linde A, Fredrikson S, Dahl H, Winberg G. HHV-6 A- or B-specific P41 antigens do not reveal virus variant-specific IgG or IgM responses in human serum. J Med Virol. 2002;66(3):394-399. (Pubitemid 34111782)
20. Cirone M, Cuomo L, Zompetta C, et al. Human herpesvirus 6 and multiple sclerosis: a study of T cell cross-reactivity to viral and myelin basic protein antigens. J Med Virol. 2002;68(2):268-272.
21. Enbom M, Linde A, Evengard B. No evidence of active infection with human herpesvirus 6 (HHV-6) or HHV-8 in chronic fatigue syndrome [letter]. J Clin Microbiol. 2000;38(6):2457.
22. Ablashi DV, Eastman HB, Owen CB, et al. Frequent HHV-6 reactivation in multiple sclerosis (MS) and chronic fatigue syndrome (CFS) patients. J Clin Virol. 2000;16(3):179-191.
23. Taus C, Pucci E, Cartechini E, et al. Absence of HHV-6 and HHV-7 in cerebrospinal fluid in relapsing-remitting multiple sclerosis. Acta Neurol Scand. 2000;101(4):224-228.
24. Ongradi J, Rajda C, Marodi CL, Csiszar A, Vecsei L. A pilot study on the antibodies to HHV-6 variants and HHV-7 in CSF of MS patients. J Neurovirol. 1999;5(5):529-532.
25. Ablashi DV, Lapps W, Kaplan M, Whitman JE, Richert JR, Pearson GR. Human herpesvirus-6 (HHV-6) infection in multiple sclerosis: a preliminary report. Mult Scler. 1998;4(6):490-496.
26. Nielsen L, Larsen AM, Munk M, Vestergaard BF. Human herpesvirus-6 immunoglobulin G antibodies in patients with multiple sclerosis. Acta Neurol Scand Suppl. 1997;169:76-78.
27. Soldan SS, Berti R, Salem N, et al. Association of human herpes virus 6 (HHV-6) with multiple sclerosis: increased IgM response to HHV-6 early antigen and detection of serum HHV-6 DNA. Nat Med. 1997;3(12):1394-1397.
28. Liedtke W, Malessa R, Faustmann PM, Eis-Hubinger AM. Human herpesvirus 6 polymerase chain reaction findings in human immunodeficiency virus associated neurological disease and multiple sclerosis. J Neurovirol. 1995;1(3-4):253-258.
29. Wilborn F, Schmidt CA, Brinkmann V, Jendroska K, Oettle H, Siegert W. A potential role for human herpesvirus type 6 in nervous system disease. J Neuroimmunol. 1994;49(1-2):213-214.
30. Sola P, Merelli E, Marasca R, et al. Human herpesvirus 6 and multiple sclerosis: survey of anti-HHV-6 antibodies by immunofluorescence analysis and of viral sequences by polymerase chain reaction. J Neurol Neurosurg Psychiatry. 1993;56(8):917-919.
31. Enbom M, Wang FZ, Fredrikson S, Martin C, Dahl H, Linde A. Similar humoral and cellular immunological reactivities to human herpesvirus 6 in patients with multiple sclerosis and controls. Clin Diagn Lab Immunol. 1999;6(4):545-549.
32. Friedman JE, Lyons MJ, Cu G, et al. The association of the human herpesvirus-6 and MS. Mult Scler. 1999;5(5):355-362.
33. Lunde MN, Gelderman AH, Hayes SL, Vogel CL. Serologic diagnosis of active toxoplasmosis complicating malignant diseases: usefulness of IgM antibodies and gel-diffusion. Cancer. 1970;25(3):637-643.
34. Patnaik M, Komaroff AL, Conley E, Ojo-Amaize EA, Peter JB. Prevalence of IgM antibodies to human herpesvirus 6 early antigen (p41/38) in patients with chronic fatigue syndrome. J Infect Dis. 1995;172(5):1364-1367.
35. Wilborn F, Schmidt CA, Zimmermann R, Brinkmann V, Neipel F, Siegert W. Detection of herpesvirus type 6 by polymerase chain reaction in blood donors: random tests and prospective longitudinal studies. Br J Haematol. 1994;88(1):187-192.
36. Ahram M, El-Omar A, Baho Y, Lubad MA. Association between human herpesvirus 6 and occurrence of multiple sclerosis among Jordanian patients. Acta Neurol Scand. 2009;120(6):430-435.
37. Alvarez-Lafuente R, de las Heras V, Garcia-Montojo M, Bartolome M, Arroyo R. Human herpesvirus-6 and multiple sclerosis: relapsing-remitting versus secondary progressive. Mult Scler. 2007;13(5):578-583.
38. Alvarez-Lafuente R, de Las Heras V, Bartolome M, Garcia-Montojo M, Arroyo R. Human herpesvirus 6 and multiple sclerosis: a one-year follow-up study. Brain Pathol. 2006;16(1):20-27.
39. Alvarez-Lafuente R, Garcia-Montojo M, de las Heras V, Bartolome M, Arroyo R. Clinical parameters and HHV-6 active replication in relapsing-remitting multiple sclerosis patients. J Clin Virol. 2006;37(suppl 1):S24-S26.
40. Hollsberg P, Kusk M, Bech E, Hansen HJ, Jakobsen J, Haahr S. Presence of Epstein-Barr virus and human herpesvirus 6B DNA in multiple sclerosis patients: associations with disease activity. Acta Neurol Scand. 2005;112(6):395-402.
41. Alvarez-Lafuente R, de las Heras V, Bartolome M, Picazo JJ, Arroyo R. Relapsing-remitting multiple sclerosis and human herpesvirus 6 active infection. Arch Neurol. 2004;61(10):1523-1527.
42. Al-Shammari S, Nelson RF, Voevodin A. HHV-6 DNAaemia in patients with multiple sclerosis in Kuwait. Acta Neurol Scand. 2003;107(2):122-124. (Pubitemid 36286801)
43. Tejada-Simon MV, Zang YC, Hong J, Rivera VM, Zhang JZ. Cross-reactivity with myelin basic protein and human herpesvirus-6 in multiple sclerosis. Ann Neurol. 2003;53(2):189-197.
44. Alvarez-Lafuente R, Martin-Estefania C, de Las Heras V, et al. Active human herpesvirus 6 infection in patients with multiple sclerosis. Arch Neurol. 2002;59(6):929-933.
45. Tejada-Simon MV, Zang YC, Hong J, Rivera VM, Killian JM, Zhang JZ. Detection of viral DNA and immune responses to the human herpesvirus 6 101-kilodalton virion protein in patients with multiple sclerosis and in controls. J Virol. 2002;76(12):6147-6154.
46. Tomsone V, Logina I, Millers A, Chapenko S, Kozireva S, Murovska M. Association of human herpesvirus 6 and human herpesvirus 7 with demyelinating diseases of the nervous system. J Neurovirol. 2001;7(6):564-569.
47. Akhyani N, Berti R, Brennan MB, et al. Tissue distribution and variant characterization of human herpesvirus (HHV)-6: increased prevalence of HHV-6A in patients with multiple sclerosis. J Infect Dis. 2000;182(5):1321-1325.
48. Goldberg SH, Albright AV, Lisak RP, Gonzalez-Scarano F. Polymerase chain reaction analysis of human herpesvirus-6 sequences in the sera and cerebrospinal fluid of patients with multiple sclerosis. J Neurovirol. 1999;5(2):134-139.
49. Mirandola P, Stefan A, Brambilla E, Campadelli-Fiume G, Grimaldi LM. Absence of human herpesvirus 6 and 7 from spinal fluid and serum of multiple sclerosis patients. Neurology. 1999;53(6):1367-1368.
50. Fillet AM, Lozeron P, Agut H, Lyon-Caen O, Liblau R. HHV-6 and multiple sclerosis [letter]. Nat Med. 1998;4(5):537.
51. Martin C, Enbom M, Soderstrom M, et al. Absence of seven human herpesviruses, including HHV-6, by polymerase chain reaction in CSF and blood from patients with multiple sclerosis and optic neuritis. Acta Neurol Scand. 1997;95(5):280-283.
52. Secchiero P, Carrigan DR, Asano Y, et al. Detection of human herpesvirus 6 in plasma of children with primary infection and immunosuppressed patients by polymerase chain reaction. J Infect Dis. 1995;171(2):273-280.
53. Alvarez-Lafuente R, Garcia-Montojo M, de Las Heras V, et al. Herpesviruses and human endogenous retroviral sequences in the cerebrospinal fluid of multiple sclerosis patients. Mult Scler. 2008;14(5):595-601.
54. Rotola A, Merlotti I, Caniatti L, et al. Human herpesvirus 6 infects the central nervous system of multiple sclerosis patients in the early stages of the disease. Mult Scler. 2004;10(4):348-354.
55. Bossolasco S, Marenzi R, Dahl H, et al. Human herpesvirus 6 in cerebrospinal fluid of patients infected with HIV: frequency and clinical significance. J Neurol Neurosurg Psychiatry. 1999;67(6):789-792.
56. Challoner 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;92(16):7440-7444.
57. McCullers JA, Lakeman FD, Whitley RJ. Human herpesvirus 6 is associated with focal encephalitis. Clin Infect Dis. 1995;21(3):571-576.
58. Mameli G, Astone V, Arru G, et al. Brains and peripheral blood mononuclear cells of multiple sclerosis (MS) patients hyperexpress MS-associated retrovirus/HERV-W endogenous retrovirus, but not Human herpesvirus 6. J Gen Virol. 2007;88(pt 1):264-274.
59. de Villiers JN, Treurnicht FK, Warnich L, Carr J, van Rensburg SJ, Kotze MJ. Analysis of viral and genetic factors in South African patients with multiple sclerosis. Metab Brain Dis. 2006;21(2-3):163-169.
60. Brudek T, Christensen T, Hansen HJ, Bobecka J, Moller-Larsen A. Simultaneous presence of endogenous retrovirus and herpes virus antigens has profound effect on cell-mediated immune responses: implications for multiple sclerosis. AIDS Res Hum Retroviruses. 2004;20(4):415-423.
61. Rotola A, Cassai E, Tola MR, Granieri E, Di Luca D. Human herpesvirus 6 is latent in peripheral blood of patients with relapsing-remitting multiple sclerosis. J Neurol Neurosurg Psychiatry. 1999;67(4):529-531.
62. Alvarez-Lafuente R, Martin-Estefania C, de las Heras V, et al. Prevalence of herpesvirus DNA in MS patients and healthy blood donors. Acta Neurol Scand. 2002;105(2):95-99.
63. Hay KA, Tenser RB. Leukotropic herpesviruses in multiple sclerosis. Mult Scler. 2000;6(2):66-68.
64. 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-S114.
65. Kim JS, Lee KS, Park JH, Kim MY, Shin WS. Detection of human herpesvirus 6 variant A in peripheral blood mononuclear cells from multiple sclerosis patients. Eur Neurol. 2000;43(3):170-173.
66. Rotola A, Caselli E, Cassai E, Tola M.R, Granieri E, Luca DD. Novel human herpesviruses and multiple sclerosis. J Neurovirol. 2000;6(suppl 2):S88-S91.
67. Mayne M, Krishnan J, Metz L, et al. Infrequent detection of human herpesvirus 6 DNA in peripheral blood mononuclear cells from multiple sclerosis patients. Ann Neurol. 1998;44(3):391-394. (Pubitemid 28421446)
68. Merelli E, Bedin R, Sola P, et al. Human herpes virus 6 and human herpes virus 8 DNA sequences in brains of multiple sclerosis patients, normal adults and children. J Neurol. 1997;244(7):450-454.
69. Torelli G, Barozzi P, Marasca R, et al. Targeted integration of human herpesvirus 6 in the p arm of chromosome 17 of human peripheral blood mononuclear cells in vivo. J Med Virol. 1995;46(3):178-188.
70. Berti R, Soldan SS, Akhyani N, McFarland HF, Jacobson S. Extended observations on the association of HHV-6 and multiple sclerosis. J Neurovirol. 2000;6(suppl 2):S85-S87.
71. Knox KK, Brewer JH, Henry JM, Harrington DJ, Carrigan DR. Human herpesvirus 6 and multiple sclerosis: systemic active infections in patients with early disease. Clin Infect Dis. 2000;31(4):894-903.
72. Soldan SS, Leist TP, Juhng KN, McFarland HF, Jacobson S. Increased lymphoproliferative response to human herpesvirus type 6A variant in multiple sclerosis patients. Ann Neurol. 2000;47(3):306-313. (Pubitemid 30141839)
73. Caserta MT, Hall CB, Schnabel K, et al. Neuroinvasion and persistence of human herpesvirus 6 in children. J Infect Dis. 1994;170(6):1586-1589.
74. Opsahl ML, Kennedy PG. Early and late HHV-6 gene transcripts in multiple sclerosis lesions and normal appearing white matter. Brain. 2005;128(pt 3):516-527.
75. Tuke PW, Hawke S, Griffiths PD, Clark DA. Distribution and quantifi- cation of human herpesvirus 6 in multiple sclerosis and control brains. Mult Scler. 2004;10(4):355-359.
76. Cermelli C, Berti R, Soldan SS, et al. High frequency of human herpesvirus 6 DNA in multiple sclerosis plaques isolated by laser microdissection. J Infect Dis. 2003;187(9):1377-1387.
77. Goodman AD, Mock DJ, Powers JM, Baker JV, Blumberg BM. Human herpesvirus 6 genome and antigen in acute multiple sclerosis lesions. J Infect Dis. 2003;187(9):1365-1376.
78. Blumberg BM, Mock DJ, Powers JM, et al. The HHV6 paradox: ubiquitous commensal or insidious pathogen? a two-step in situ PCR approach. J Clin Virol. 2000;16(3):159-178.
79. Coates AR, Bell J. HHV-6 and multiple sclerosis. Nat Med. 1998;4(5):537-538.
80. Sanders VJ, Felisan S, Waddell A, Tourtellotte WW. Detection of herpesviridae in postmortem multiple sclerosis brain tissue and controls by polymerase chain reaction. J Neurovirol. 1996;2(4):249-258.