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. 2002 Mar 12;12(2):107–113. doi: 10.1002/rmv.347

Viruses and autoimmunity: an affair but not a marriage contract

Barry T Rouse 1,✉, Shilpa Deshpande 1
PMCID: PMC7169138  PMID: 11921306

Abstract

Viruses are considered as causative agents and contributors to lesion expression in autoimmune disease, notions best supported by studies in animal model systems. This review discusses relationships between virus infection and autoimmunity focusing on mechanisms by which they could induce autoreactivity. The popular idea of molecular mimicry is viewed skeptically with the reviewers taking the viewpoint that viruses contribute to autoimmunity mainly by inducing several nonspecific inflammatory events that together are sufficient to trigger autoreactivity in genetically receptive hosts. Copyright © 2002 John Wiley & Sons, Ltd.

REFERENCES

  • 1. Wilson DB, Pinilla C, Wilson DH, Houghton RA. Immunogenicity. I. Use of peptide libraries to identify epitopes that activate clonotypic CD4+ T cells and induce T cell responses to native peptide ligands. J Immunol 1999; 163: 6424–6434. [PubMed] [Google Scholar]
  • 2. Mason D. A very high level of crossreactivity is an essential feature of the T‐cell receptor. Immunol Today 1998; 19: 395–404. [DOI] [PubMed] [Google Scholar]
  • 3. Vyse TJ, Todd JA. Genetic analysis of autoimmune disease. Cell 1996; 85: 311–318. [DOI] [PubMed] [Google Scholar]
  • 4. Kumar D, et al North American twins with IDDM. Genetic etiological and clinical significance of disease concordance according to age, zygosity and the interval after diagnosis in first twins. Diabetes 1993; 42: 1351–1363. [DOI] [PubMed] [Google Scholar]
  • 5. McFarland HF. Twin studies and multiple sclerosis. Ann Neurol 1992; 32: 722–723. [DOI] [PubMed] [Google Scholar]
  • 6. Olson JK, Croxford JL, Miller SD. Virus‐induced autoimmunity: potential role of viruses in initiation, perpetuation and progression of T‐cell mediated autoimmune disease. Viral Immunol 2001; 14: 227–250. [DOI] [PubMed] [Google Scholar]
  • 7. Oldstone MBA. Molecular mimicry and immune mediated disease. FASEB J 1998; 12: 1255–1265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8. Wucherpfennig KW. Mechanisms for the induction of autoimmunity by infectious agents. J Clin Invest 2001; 108: 1097–1104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9. Fujinami RS. Viruses and autoimmune disease – two sides to a coin. Trends Microbiol 2001; 9: 377–381. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10. Whitton JL, Fujinami RS. Viruses as triggers of autoimmunity: facts and fantasies. Curr Opin Microbiol 1999; 2: 392–397. [DOI] [PubMed] [Google Scholar]
  • 11. Soldan SS, 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: 1394–1397. [DOI] [PubMed] [Google Scholar]
  • 12. Yoon JW, Onodera T, Notkins AL. Virus induced beta cell damage and insulin dependent hyperglycaemia in mice infected with Coxsackie virus B4. J Exp Med 1978; 148: 1068–1080. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13. Clements GB, Galbrath DN, Taylor KW. Coxsackie B virus and onset of childhood diabetes. Lancet 1995; 346: 221–223. [DOI] [PubMed] [Google Scholar]
  • 14. Ginsberg‐Fellner F, et al Diabetes mellitus and autoimmunity in patients with congenital rubella syndrome. Rev Infect Dis 1985; 7 Suppl: S170–S176. [DOI] [PubMed] [Google Scholar]
  • 15. James JA, Harley JB. B‐cell epitope spreading in autoimmunity. Immunol Res 1998; 164: 185–200. [DOI] [PubMed] [Google Scholar]
  • 16. Romero PM, et al Rhuematologic and autoimmune manifestations in patients with chronic hepatitis C virus infection. Rev Esp Enfern Diag 1997; 89: 591–598. [PubMed] [Google Scholar]
  • 17. Fujinami RS, et al Molecular mimicry in virus infection: cross reaction of measle virus phosphoprotein and herpes simplex virus protein with human intermediate filaments. Proc Natl Acad Sci U S A 1983; 80: 2346–2350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18. Mavesakil E, Elzen P, Sercarz EE. Self reactive T cell and degeneracy of T cell recognition: Evolving concepts – from sequence homology to shape mimicry and TCR flexibility. Autoimmunity 2001; 16: 201–209. [DOI] [PubMed] [Google Scholar]
  • 19. Benoist C, Mathis D. Autoimmunity provoked by infection: How good is the case for T cell epitope mimicry? Nature Immunol 2001; 2: 797–801. [DOI] [PubMed] [Google Scholar]
  • 20. Oldstone MBA, Nerenberg M, Southern P, Price J, Lewicki H. Virus infection triggers insulin dependent diabetes mellitus in a transgenic model. Role of antiself immune response. Cell 1991; 65: 319–331. [DOI] [PubMed] [Google Scholar]
  • 21. Ohashi P, et al Ablation of tolerance and induction of diabetes by virus infection in viral antigen transgenic mice. Cell 1991; 65: 305–317. [DOI] [PubMed] [Google Scholar]
  • 22. Evans CF, Horwitz MS, Hobbs MF, Oldstone MBA. Viral infection of transgenic mice expressing a viral protein in oligodendroglocytes leads to chronic central nervous system autoimmune disease. J Exp Med 1996; 184: 2371–2384. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23. Von Herrath MG, Guerde S, Lewicki H, Flavell RA, Oldstone MBA. Coexpression of B7.1 and viral (self) transgene in pancreatic β cells can break peripheral ignorance and lead to spontaneous autoimmune diabetes. Immunity 1995; 3: 727–738. [DOI] [PubMed] [Google Scholar]
  • 24. Campbell I, et al Islet inflammation and hyperplasia induced by the pancreatic islet specific overexpression of IL‐6 in transgenic mice. Am J Pathol 1994; 145: 157–166. [PMC free article] [PubMed] [Google Scholar]
  • 25. Sarvetnick N, et al Insulin dependent diabetes mellitus induced in transgenic mice by ectopic expression of class II MHC and interferon gamma. Cell 1998; 52: 773–782. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26. Olson JK, et al A virus‐induced molecular mimicry model of multiple sclerosis. J Clin Invest 2001; 108: 311–318. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27. Theil DJ, et al Virus can silently prime for and trigger central nervous system autoimmune disease. J Neurovirol 2001; 7: 220–227. [DOI] [PubMed] [Google Scholar]
  • 28. Panoutsakopoulou V, Cantor H. On the relationship between viral infection and autoimmunity. J Autoimmunity 2001; 16: 341–345. [DOI] [PubMed] [Google Scholar]
  • 29. Dawson C, Togni B. Herpes simplex eye infections. Clinical manifestation, pathogenesis and management. Eur Ophthalmol 1976; 21: 11–29. [DOI] [PubMed] [Google Scholar]
  • 30. Cantor H. T‐cell receptor crossreactivity and autoimmune disease. Adv Immunol 2000; 75: 209–233. [DOI] [PubMed] [Google Scholar]
  • 31. Panoutsakopoulou V. Analysis of the relationship between viral induction and autoimmune disease. Immunity 2001; 15: 137–147. [DOI] [PubMed] [Google Scholar]
  • 32. Despande S, et al Herpes simplex virus induced keratitis: evaluation of the role of molecular mimicry in lesion pathogenesis. J Virol 2001; 75: 3077–3088. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33. Streilen JW, Dana MR, Ksander BR. Immunity causing blindness: five different paths to herpes stromal keratitis. Immunol Today 1997; 18: 443–449. [DOI] [PubMed] [Google Scholar]
  • 34. Horwitz MS, Fine C, Ilic A, Sarvetnick N. Requirements of viral‐mediated autoimmune diabetes: β‐cell damage and immune infiltration. J Autoimmunity 2001 2001; 16: 211–217. [DOI] [PubMed] [Google Scholar]
  • 35. Miller SD, et al Persistant infection with Theiler's viruses leads to autoimmunity via epitope spreading. Nat Med 1997; 3: 1133–1136. [DOI] [PubMed] [Google Scholar]
  • 36. Gangappa S, Babu JS, Thomas J, Daheshia M, Rouse BT. Virus induced immunoinflammatory lesions in the absence of viral antigen recognition. J Immunol 1998; 61: 4289–4300. [PubMed] [Google Scholar]
  • 37. Kotzin BC, Leung DY, Kappler J, Marrack P. Superantigens and their potential role in human disease. Adv Immunol 1993; 55: 99–166. [DOI] [PubMed] [Google Scholar]
  • 38. Ferri C, Zignego AL. Relation between infection and autoimmunity in mixed cryoglobulinemia. Curr Opin Rheumatol 2000; 12: 53–60. [DOI] [PubMed] [Google Scholar]

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