Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Immunology of Neurodevelopmental Disorders
  • Published:

Association of chronic progressive neurological disease and ubiquitous viral agents: lessons from human herpesvirus 6 and multiple sclerosis

Molecular Psychiatry volume 7, pages S29–S31 (2002)Cite this article

Multiple sclerosis (MS) is a common neurological disorder characterized by inflammation and plaque formation in the white matter of the brain. It is generally considered to have an autoimmune component influenced by both genetic and environmental factors. We have investigated the ubiquitous human herpes virus 6 (HHV-6) and its possible role in the etiology and immunopathology of MS. The immune response against HHV-6 is different in MS patients compared to controls. MS patients have increased levels of anti-HHV-6 IgM in serum and CSF,1 indicating a re-infection, a persistent infection or a reactivation of the virus. They also have higher lymphoproliferative responses and a higher T cell precursor frequency against the A variant of HHV-6,2 suggesting an active virus-specific immune response. In addition to these virus-specific humoral and cellular immune responses we detect viral DNA in serum, urine and plaques from MS patients.3 Previous studies have suggested that the presence of serum HHV-6 DNA is reflective of active replication of the virus.4 These data support an association between HHV-6 infection and MS. Whether or not the virus is a causative agent of this disease still remains to be proven.

Multiple sclerosis is the most prevalent demyelinating disease in humans, affecting over 350 000 Americans. The clinical neurological symptoms are consistent with damage to the white matter tracts within the central nervous system (CNS). The course of the disease can vary from the most common relapsing-remitting form to primary progressive cases. Neuropathologically the hallmark of this disease is plaque formation in the CNS. The presence of myelin reactive T and B cells at the site of inflammation in the brain suggests that autoimmune mechanisms are involved in the pathogenesis of the disease.5 While there are clear genetic influences associated with MS, environmental factors have also been suggested to play a role. For many years, an infectious etiology of MS has been suspected as it fits with a number of epidemiological observations. These include: (1) epidemiological evidence of childhood exposure to infectious agents and an increase in disease exacerbations with viral infection;6,7 (2) geographic association of disease susceptibility with evidence of MS clustering;8,9 (3) evidence that migration to and from high risk areas influences the likelihood of developing MS;7,10 (4) abnormal immune responses to a variety of viruses;11,12 and (5) analogy with animal models and other human diseases in which viruses can cause diseases with a relapsing remitting course and demyelination after long incubation periods. However, no virus to date has been definitively shown to be the sole agent that is the ‘cause’ of MS. After many years of intensive research the etiology of this disorder is still unknown.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Soldan SS et al. Nat Med 1997 3: 1394–1397

  2. Soldan SS et al. Ann Neurol 2000 47: 306–313

  3. Akhyani N et al. J Infect Dis 2000 182: 1321–1325

  4. Secchiero P et al. J Infect Dis 1995 171: 273–280

  5. Lassmann H . In: Compston A et al (eds) McAlpine's Multiple Sclerosis Churchill Livingstone: London 1998 323–358

    Google Scholar 

  6. Johnson RT . Ann Neurol 1994 36: S54–S60

  7. Weinshenker BG . Neurol Clin 1996 14: 291–308

  8. Haahr S et al. Lancet 1997 349: 923

  9. Kurtzke JF . Acta Neurol Scand Suppl 1995 161: 23–33

  10. Alter M et al. Arch Neurol 1996 15: 234–237

  11. Neighbour PA et al. Neurology 1981 31: 561–566

  12. Jacobson S et al. J Exp Med 1985 162: 839–850

  13. Sola P et al. J Neurol Neurosurg Psychiatry 1993 56: 917–919

  14. Challoner PB et al. Proc Natl Acad Sci U S A 1995 92: 7440–7444

  15. Braun DK et al. Clin Microbiol Rev 1997 10: 521–567

  16. Nagai M, Jacobson S . Curr Opin Neurol 2001 14: 381–386

  17. Blumberg BM et al. Clin Virol 2000 16: 159–178

  18. Lorenzo ME et al. Semin Immunol 2001 13: 1–9

  19. Lucchinetti C et al. Brain 1999 122: 2279–2295

  20. Pinter C et al. J Neurovirol 2000 6 (Suppl 2): S42–S46

  21. Spiller OB et al. J Infect Dis 1997 176: 339–347

  22. Montefiori DC et al. Virology 1994 205: 82–92

  23. Söderberg Naucler CS et al. Immunol Rev 1996 152: 175–192

  24. Wilborn F et al. J Neuroimmunol 1994 49: 213–214

  25. Ablashi DV et al. Mult Scler 1998 4: 490–496

  26. Enborm M et al. Clin Diagn Lab Immunol 1999 6: 545–549

  27. Albashi DV et al. J Clin Virol 2000 16: 179–191

  28. Friedman JE et al. Mult Scler 1999 5: 355–362

  29. Snbom M et al. J Med Virol 2000 62: 498–504

  30. Ongradi J et al. J Neurovirol 1999 5: 529–532

Download references

Author information

Authors and Affiliations

  1. Neuroimmunology Branch, National institute of Neurological Disorders and Stroke, National Institute of Health, Bethesda, 20892, MD, USA

    A Fogdell-Hahn, S S Soldan & S Jacobson

Authors
  1. A Fogdell-Hahn
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S S Soldan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S Jacobson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S Jacobson.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fogdell-Hahn, A., Soldan, S. & Jacobson, S. Association of chronic progressive neurological disease and ubiquitous viral agents: lessons from human herpesvirus 6 and multiple sclerosis. Mol Psychiatry 7 (Suppl 2), S29–S31 (2002). https://doi.org/10.1038/sj.mp.4001172

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.mp.4001172

This article is cited by

Search

Advanced search

Quick links