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. 2002 Aug 12;68(2):268–272. doi: 10.1002/jmv.10190

Human herpesvirus 6 and multiple sclerosis: A study of t cell cross‐reactivity to viral and myelin basic protein antigens

Mara Cirone 1, Laura Cuomo 2, Claudia Zompetta 1, Stefano Ruggieri 2,3, Luigi Frati 1,2, Alberto Faggioni 1, Giuseppe Ragona 1,2,
PMCID: PMC7167112  PMID: 12210418

Abstract

Several reports have suggested an association of human herpesvirus 6 (HHV‐6) with multiple sclerosis. Autoreactive T lymphocytes directed against myelin components seem to contribute to the pathogenesis of the disease. It has been suggested that molecular mimicry between viral and self‐antigens might be one of the mechanisms that determine the onset of several autoimmune diseases. Following this hypothesis, the purpose of the present study was to evaluate if HHV‐6 could play a role in activating T cells capable of cross‐reaction with an important myelin component, the myelin basic protein. T cell lines were established from 22 multiple sclerosis patients and from 16 healthy controls, and their capability to react to both virus and myelin basic protein antigens was compared. The analysis of T cell cross‐reactivity in patients and controls did not show significant differences in the HHV‐6 ability to activate myelin basic protein‐reactive T cells. Similarly, the evaluation of the humoral immune response to HHV‐6 in patients and controls did not mirror any abnormality in the HHV‐6 status in multiple sclerosis patients. Therefore, although the findings of activity in vitro of T cell lines with dual specificity are consistent with the hypothesis of molecular mimicry, the lack of differences in cross‐reactivity between patients and controls do not support molecular mimicry as an important mechanism in the physiopathology of this disease. J. Med. Virol. 68: 268–272, 2002. © 2002 Wiley‐Liss, Inc.

Keywords: molecular mimicry, T lymphocyte, herpesvirus, demyelinating disease

REFERENCES

  1. Ablashi DV, Lapps W, Kaplan M, Whitman JE, Richert JR, Pearson GR. 1998. Human herpesvirus 6 (HHV‐6) infection in multiple sclerosis: a preliminary report. Multiple sclerosis 4: 490–496. [DOI] [PubMed] [Google Scholar]
  2. Akhyani N, Berti R, Brennan MB, Soldan SS, Eaton JM, McFarland HF, Jacobson S. 2000. Tissue distribution and variant characterization of human herpesvirus (HHV)‐6: increased prevalence of HHV‐6 A in patients with multiple sclerosis. J Inf Dis 182: 1321–1325. [DOI] [PubMed] [Google Scholar]
  3. Challoner PB, Smith KT, Parker JD, MacLeod DL, Coulter SN, Rose TM, Schiltz ER, Bennett JL, Garber RL, Chang M, Schad PA, Stewart PM, Nowinsky RC, Beown JP, Burner GL. 1995. Plaque‐associated expression of human herpesvirus 6 in multiple sclerosis. Proc Natl Acad Sci USA 92: 7440–7444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Clark DA. 2000. Human herpesvirus 6. Rev Med Virol 10: 155–173. [DOI] [PubMed] [Google Scholar]
  5. Coates ARM, Bell J. 1998. HHV‐6 and multiple sclerosis. Nat Med 4: 537–538. [DOI] [PubMed] [Google Scholar]
  6. Cuomo L, Trivedi P, Cardillo MR, Gagliardi FM, Vecchione A, Caruso R, Calogero A, Frati L, Faggioni A, Ragona G. 2001. Human herpesvirus 6 (HHV‐6) infection in neoplastic and normal brain tissue. J Med Virol 63: 45–51. [PubMed] [Google Scholar]
  7. Enbom M, Wang FZ, Fredrikson S, Msrtin C, Dahl H, Linde A. 1999. Similar humoral and cellular immunological reactivities to human herpesvirus 6 in patients with multiple sclerosis and controls. Clin Diagn Lab Immunol 6: 545–549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fillet AM, Lozeron P, Agut H, Lyon‐Caen O, Liblau R. 1998. HHV‐6 and multiple sclerosis. Nat Med 4: 537. [DOI] [PubMed] [Google Scholar]
  9. Gautam AM, Liblau R, Chelvanayagam G, Steinman L, Boston T. 1998. A viral peptide with limited homology to a self peptide can induce clinical signs of experimental autoimmune encephalomyelitis. J Immunol 161: 60–64. [PubMed] [Google Scholar]
  10. Jacobson S, Soldan SS, Berti R. 1998. HHV‐6 and multiple sclerosis. Nat Med 4: 538. [PubMed] [Google Scholar]
  11. Knox KK, Brewer JH, Henry JM, Harrington DJ, Carrigan DR. 2000. Human herpesvirus 6 and multiple sclerosis: systemic active infections in patients with early disease. Clin Infect Dis 31: 894–903. [DOI] [PubMed] [Google Scholar]
  12. Lyall EGH, Cubie HA. 1995. Human herpesvirus 6 DNA in the saliva of pediatric oncology patients and controls. J Med Virol 47: 317–322. [DOI] [PubMed] [Google Scholar]
  13. Mayne M, Krishnan J, Metz L, Nath A, Auty A, Sahai BM, Power C. 1998. Infrequent detection of human herpesvirus 6 DNA in peripheral blood mononuclear cells from multiple sclerosis patients. Ann Neurol 44: 391–394. [DOI] [PubMed] [Google Scholar]
  14. Morris‐Downes MM, McCormack K, Baker D, Sivaprasad D, Natkunarajah J, Amor S. 2002. Encephalitogenic and immunogenic potential of mylein‐associated glycoprotein (MAG), oligondendrocyte‐specific glycoprotein (OSP) and 2′, 3′‐cyclic nucleotide 3′‐phosphodiesterase (CNPase) in ABH and SJL mice. J Neuroimmunol 122: 20–33. [DOI] [PubMed] [Google Scholar]
  15. Noseworthy JH, Lucchinetti C, Rodriguez M, Weishenker BG. 2000. Multiple sclerosis. N Engl J Med 343: 938–952. [DOI] [PubMed] [Google Scholar]
  16. Soldan S, Berti S, Salem N, Secchiero P, Flamand L, Calabresi PA, Brennan MB, Maloni HW, McFarland HF, Lin HH, Patnaik M, Jacobson S. 1997. 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 3: 1394–1398. [DOI] [PubMed] [Google Scholar]
  17. Soldan SS, Leist TP, Juhng KN, McFarland HF, Jacobson S. 2000. Increased lymphoproliferative response to Human Herpesvirus type 6A variant in multiple sclerosis patients. Ann Neurol 47: 306–313. [PubMed] [Google Scholar]
  18. Steinman L, Oldstone MBA. 1997. More mayhem from molecular mimics. Nature Med 12: 1321–1322. [DOI] [PubMed] [Google Scholar]
  19. Talbot PJ, Paquette JS, Ciurli C, Antel JP, Ouellet F. 1996. Myelin basic protein and human coronavirus 229E cross‐reactive T cells in multiple sclerosis. Ann Neurol 39: 233–240. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Van Noort JM, Bajramovic JJ, Plomp AC, van Stipdonk MJB. 2000. Mistaken self, a novel model that links microbial infections with myelin‐directed autoimmunity in multiple sclerosis. J Neuroimmunol 105: 46–57. [DOI] [PubMed] [Google Scholar]
  21. Wucherpfennig K, Strominger J. 1995. Molecular mimicry in T cell‐mediated autoimmunity: viral peptides activate human T cell clones specific for myelin basic protein. Cell 80: 695–705. [DOI] [PMC free article] [PubMed] [Google Scholar]

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