Skip to main content
Elsevier - PMC COVID-19 Collection logoLink to Elsevier - PMC COVID-19 Collection
. 2002 Jul 25;24(10):73–76. doi: 10.1016/S0196-4399(02)80019-8

Are virus infections triggers for autoimmune disease?

Jane E Libbey 1, Robert S Fujinami 1,1
PMCID: PMC7135185  PMID: 32287669

Abstract

Viruses have been implicated in the initiation, progression, and exacerbation of several human autoimmune diseases, including multiple sclerosis. However, no single virus has been demonstrated as the etiologic agent. Multiple different infections may be involved, first in priming the immune system for autoimmunity and then in triggering the actual disease. A model based on experimental allergic encephalomyelitis, an animal model of multiple sclerosis, has been developed, which shows that an initial early infection with a virus having molecular mimicry to self-epitopes can prime for disease that occurs after a subsequent non-specific immunologic stimulus, such as a different infection. The role of multiple infections in the development of autoimmune disease may explain why no one virus has been implicated.

References

  • 1.Mackay I.R., Van de Water J., Gershwin M.E. Autoimmunity. Thoughts for the millennium. Clin. Rev. Allergy Immunol. 2000;18:87–117. doi: 10.1385/criai:18:1:87. [DOI] [PubMed] [Google Scholar]
  • 2.Sakaguchi S. Animal models of autoimmunity and their relevance to human diseases. Curr. Opin. Immunol. 2000;12:684–690. doi: 10.1016/s0952-7915(00)00163-1. [DOI] [PubMed] [Google Scholar]
  • 3.Fujinami R.S. Molecular mimicry in virus infection: crossreaction of measles virus phosphoprotein or of herpes simplex virus protein with human intermediate filaments. Proc. Natl. Acad. Sci. USA. 1983;80:2346–2350. doi: 10.1073/pnas.80.8.2346. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Oldstone M.B.A. Molecular mimicry and autoimmune disease. Cell. 1987;50:819–820. doi: 10.1016/0092-8674(87)90507-1. [DOI] [PubMed] [Google Scholar]
  • 5.Barnett L.A., Fujinami R.S. Molecular mimicry: a mechanism for autoimmune injury. FASEB J. 1992;6:840–844. doi: 10.1096/fasebj.6.3.1740233. [DOI] [PubMed] [Google Scholar]
  • 6.Oldstone M.B.A. Molecular mimicry and immune-mediated diseases. FASEB J. 1998;12:1255–1265. doi: 10.1096/fasebj.12.13.1255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Zhao Z.S. Molecular mimicry by herpes simplex virus-type 1: autoimmune disease after viral infection. Science. 1998;279:1344–1347. doi: 10.1126/science.279.5355.1344. [DOI] [PubMed] [Google Scholar]
  • 8.Liang B., Mamula M.J. Molecular mimicry and the role of B lymphocytes in the processing of autoantigens. Cell Mol. Life Sci. 2000;57:561–568. doi: 10.1007/PL00000718. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Lehmann P.V. Spreading of T-cell autoimmunity to cryptic determinants of an autoantigen. Nature. 1992;358:155–157. doi: 10.1038/358155a0. [DOI] [PubMed] [Google Scholar]
  • 10.Farris A.D. Epitope mimics and determinant spreading: pathways to autoimmunity. Cell Mol. Life Sci. 2000;57:569–578. doi: 10.1007/PL00000719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Miller S.D. Persistent infection with Theiler's virus leads to CNS autoimmunity via epitope spreading. Nat. Med. 1997;3:1133–1136. doi: 10.1038/nm1097-1133. [DOI] [PubMed] [Google Scholar]
  • 12.Tough D.F., Borrow P., Sprent J. Induction of bystander T cell proliferation by viruses and type I interferon in vivo. Science. 1996;272:1947–1950. doi: 10.1126/science.272.5270.1947. [DOI] [PubMed] [Google Scholar]
  • 13.Horwitz M.S. Diabetes induced by Coxsackie virus: initiation by bystander damage and not molecular mimicry. Nat. Med. 1998;4:781–785. doi: 10.1038/nm0798-781. [DOI] [PubMed] [Google Scholar]
  • 14.Theil D.J. Viruses can silently prime for and trigger central nervous system autoimmune disease. J. Neurovirol. 2001;7:220–227. doi: 10.1080/13550280152403263. [DOI] [PubMed] [Google Scholar]
  • 15.von Herrath M.G., Oldstone M.B.A. Interferon-γ is essential for destruction of β cells and development of insulin-dependent diabetes mellitus. J. Exp. Med. 1997;185:531–539. doi: 10.1084/jem.185.3.531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Sarvetnick N. Etiology of autoimmunity. Immunol. Res. 2000;21:357–362. doi: 10.1385/IR:21:2-3:357. [DOI] [PubMed] [Google Scholar]
  • 17.Cunningham M.W., Krisher K., Graves D.C. Murine monoclonal antibodies reactive with human heart and group A streptococcal membrane antigens. Infect. Immun. 1984;46:34–41. doi: 10.1128/iai.46.1.34-41.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Dayan C.M., Daniels G.H. Chronic autoimmune thyroiditis. N. Engl. J. Med. 1996;335:99–107. doi: 10.1056/NEJM199607113350206. [DOI] [PubMed] [Google Scholar]
  • 19.Magnusson V. Cytokine polymorphisms in systemic lupus erythematosus and Sjogren's syndrome. Scand J. Immunol. 2001;54:55–61. doi: 10.1046/j.1365-3083.2001.00965.x. [DOI] [PubMed] [Google Scholar]
  • 20.Kamradt T., Mitchison N.A. Tolerance and autoimmunity. N. Engl. J. Med. 2001;344:655–664. doi: 10.1056/NEJM200103013440907. [DOI] [PubMed] [Google Scholar]
  • 21.Mackay I.R. Science, medicine, and the future: tolerance and autoimmunity. BMJ. 2000;321:93–96. doi: 10.1136/bmj.321.7253.93. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Xiao B.G., Link H. Antigen-specific T cells in autoimmune diseases with a focus on multiple sclerosis and experimental allergic encephalomyelitis. Cell Mol. Life Sci. 1999;56:5–21. doi: 10.1007/s000180050002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Anderson D.W. Revised estimate of the prevalence of multiple sclerosis in the United States. Ann. Neurol. 1992;31:333–336. doi: 10.1002/ana.410310317. [DOI] [PubMed] [Google Scholar]
  • 24.Lucchinetti C.F. Distinct patterns of multiple sclerosis pathology indicates heterogeneity on pathogenesis. Brain Pathol. 1996;6:259–274. doi: 10.1111/j.1750-3639.1996.tb00854.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Lublin F.D., Reingold S.C. Defining the clinical course of multiple sclerosis: results of an international survey. Neurology. 1996;46:907–911. doi: 10.1212/wnl.46.4.907. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. [DOI] [PubMed] [Google Scholar]
  • 26.Kurtzke J.F., Heltberg A. Multiple sclerosis in the Faroe Islands: an epitome. J. Clin. Epidemiol. 2001;54:1–22. doi: 10.1016/s0895-4356(00)00268-7. [DOI] [PubMed] [Google Scholar]
  • 27.Kurtzke J.F. In: The epidemiology of multiple sclerosis. Raine C.S., McFarland H.F., Tourtellotte W.W., editors. Chapman & Hall; London: 1997. pp. 91–140. (Multiple sclerosis: clinical and pathogenetic basis). [Google Scholar]
  • 28.Kurtzke J.F. Epidemiologic evidence for multiple sclerosis as an infection. Clin. Microbiol. Rev. 1993;6:382–427. doi: 10.1128/cmr.6.4.382. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Johnson R.T. Chronic inflammatory and demyelinating diseases. Lippincott-Raven; Philadelphia and New York: 1998. p. 227. (Viral infections of the nervous system). [Google Scholar]
  • 30.Sibley W.A., Bamford C.R., Clark K. Clinical viral infections and multiple sclerosis. Lancet. 1985;1:1313–1315. doi: 10.1016/S0140-6736(85)92801-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Andersen O. Viral infections trigger multiple sclerosis relapses: a prospective seroepidemiological study. J. Neurol. 1993;240:417–422. doi: 10.1007/BF00867354. [DOI] [PubMed] [Google Scholar]
  • 32.De Keyser J., Zwanikken C., Boon M. Effects of influenza vaccination and influenza illness on exacerbations in multiple sclerosis. J. Neurol. Sci. 1998;159:51–53. doi: 10.1016/s0022-510x(98)00139-7. [DOI] [PubMed] [Google Scholar]
  • 33.Panitch H.S. Influence of infection on exacerbations of multiple sclerosis. Ann. Neurol. 1994;36:S25–S28. doi: 10.1002/ana.410360709. (Suppl.) [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Fazakerley J.K., Amor S., Nash A.A. In: Animal model systems of MS. Russell W.C., editor. John Wiley & Sons, Ltd; London: 1997. pp. 255–273. (Molecular biology of multiple sclerosis). [Google Scholar]
  • 35.Fazakerley J.K., Buchmeier M.J. Pathogenesis of virus-induced demyelination. Adv. Virus Res. 1993;42:249–324. doi: 10.1016/S0065-3527(08)60087-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Atkins G.J. Analysis of the molecular basis of neuropathogenesis of RNA viruses in experimental animals: relevance for human disease? Neuropathol. Appl. Neurobiol. 1994;20:91–102. doi: 10.1111/j.1365-2990.1994.tb01167.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.Watanabe R., Wege H., ter Meulen V. Adoptive transfer of EAE-like lesions from rats with coronavirus-induced demyelinating encephalomyelitis. Nature. 1983;305:150–153. doi: 10.1038/305150a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Tsunoda I., Fujinami R.S. Two models for multiple sclerosis: experimental allergic encephalomyelitis and Theiler's murine encephalomyelitis virus. J. Neuropathol. Exp. Neurol. 1996;55:673–686. doi: 10.1097/00005072-199606000-00001. [DOI] [PubMed] [Google Scholar]
  • 39.Fazekas F. The contribution of magnetic resonance imaging to the diagnosis of multiple sclerosis. Neurology. 1999;53:448–456. doi: 10.1212/wnl.53.3.448. [DOI] [PubMed] [Google Scholar]
  • 40.Miller D.H. Magnetic resonance imaging in monitoring the treatment of multiple sclerosis: concerted action guidelines. J. Neurol. Neurosurg. Psychiatry. 1991;54:683–688. doi: 10.1136/jnnp.54.8.683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41.Miller D.H. Guidelines for the use of magnetic resonance techniques in monitoring the treatment of multiple sclerosis. Ann. Neurol. 1996;39:6–16. doi: 10.1002/ana.410390104. U.S. National MS Society Task Force. [DOI] [PubMed] [Google Scholar]

Articles from Clinical Microbiology Newsletter are provided here courtesy of Elsevier

RESOURCES