Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

A search for the presence of the enteroviral capsid protein VP1 in pancreases of patients with Type 1 (insulin-dependent) diabetes and pancreases and hearts of infants who died of coxsackieviral myocarditis

  • 132 Accesses

  • 98 Citations


Using an antiserum raised to a recombinant coxsackie virus B3 capsid protein, VP1, an immunocytochemical technique was developed which was capable of detecting the presence of all coxsackie B viruses in formalin fixed paraffin embedded infected tissue culture cells. This technique was tested on autopsy heart and pancreas from 21 patients who were thought to have died of acute coxsackievirus B myocarditis. Cardiac myocytes were positive for the VP1 protein in 12 of 20 cases where the heart was available for study. Insulitis was present in the pancreas in seven of these cases and in all seven islet endocrine cells containing VP1 were found. VP1 was only rarely found in exocrine pancreas. In heart and pancreas, cells shown to contain VP1 usually showed signs of necrosis. Autopsy pancreases from 88 patients who had died at clinical presentation of Type 1 (insulin-dependent) diabetes mellitus showed no evidence of the presence of VP1. The continuing destruction of insulin-secreting B cells seen at the time of death in the diabetic pancreas is unlikely to be due to a direct cytopathic effect of a coxsackie B virus. However, this study does not exclude the possibility that a persistent infection of B cells by a defective enterovirus may result in their destruction by an autoimmune mechanism.


  1. 1.

    Wolf E, Spencer KM, Cudworth AG (1983) The genetic susceptibility to Type 1 (insulin-dependent) diabetes: analysis of the HLA-DR association. Diabetologia 24: 224–230

  2. 2.

    Todd JA, Bell JI, McDevitt HO (1987) HLA-DQβ gene contributes to susceptibility and resistence to insulin-dependent diabetes mellitus. Nature 329: 599–604

  3. 3.

    Tattershall RB, Pyke DA (1972) Diabetes in Identical Twins. Lancet II: 1120–1125

  4. 4.

    Banatvala JE, Bryant J, Schernthaner G, Borkenstein M, Schober E, Brown D, De Silva LM, Menser MA, Silink M (1985) Coxsackie B, Mumps, Rubella, and Cytomegalovirus specific IgM responses in patients with juvenile-onset insulin-dependent diabetes mellitus in Britain, Austria and Australia. Lancet I: 1409–1412

  5. 5.

    Yoon JW, Austin M, Onodera T, Notkins AL (1979) Virus induced diabetes mellitus. N Engl J Med 300: 1173–1179

  6. 6.

    Gladisch R, Hofmann W, Waldherr R (1976) Myokarditis und Insulitis nach Coxsackie-Virus-Infekt. Z Kardiol 65: 837–849

  7. 7.

    Ujevich MM, Jaffe R (1980) Pancreatic Islet Cell Damage. Its occurence in neonatal Coxsackie virus encephalomyocarditis. Arch Path Lab Med 104: 438–441

  8. 8.

    Jenson AB, Rosenberg HS, Notkins AL (1980) Pancreatic islet-cell damage in children with fatal viral infections. Lancet II: 354–358

  9. 9.

    Bottazzo GF, Dean BM, Mcnally JM, MacKay EH, Swift PGF, Gamble DR (1985) In situ characterization of autoimmune phenomena and expression of HLA molecules in the pancreas in diabetic insulitis. N Engl J Med 313: 353–360

  10. 10.

    Foulis AK, Farquharson MA (1986) Aberrant expression of HLA-DR antigens by insulin containing beta cells in recent onset Type 1 (insulin-dependent) diabetes mellitus. Diabetes 35: 1215–1224

  11. 11.

    Foulis AK, Farquharson MA, Hardman R (1987) Aberrant expression of Class II major histocompatibility complex molecules by B cells and hyperexpression of Class I major histocompatibility complex molecules by insulin containing islets in Type I (insulin-dependent) diabetes mellitus. Diabetologia 30: 333–343

  12. 12.

    Foulis AK, Farquharson MA, Meager A (1987) Immunoreactive alpha-interferon in insulin-secreting beta cells in Type 1 diabetes mellitus. Lancet II: 1423–1427

  13. 13.

    Foulis AK, Jackson R, Farquharson MA (1988) The pancreas in idiopathic Addison's disease — a search for a prediabetic pancreas. Histopathology 12: 481–490

  14. 14.

    Werner S, Klump WM, Schönke H, Hofscheider PH, Kandolf R (1988) Expression of coxsackievirus B3 capsid proteins in Escherichia coli and generation of virus-specific antisera. DNA 7: 307–316

  15. 15.

    Yousef GE, Bell EJ, Mann GF, Murugesan V, Smith DG, McCartney RA, Mowbray JF (1988) Chronic enterovirus infection in patients with postviral fatigue syndrome. Lancet I: 146–150

  16. 16.

    Bowles NE, Richardson PJ, Olsen EGJ, Archard LC (1986) Detection of Coxsackie-B-virus-specific RNA sequences in myocardial biopsy samples from patients with myocarditis and dilated cardiomyopathy. Lancet I: 1120–1122

  17. 17.

    Kandolf R (1988) The impact of recombinant DNA technology on the study of enterovirus heart disease. In: Bendinelli M, Friedman H (eds) Coxsackieviruses — a general update. Plenum, New York, pp 293–318

  18. 18.

    Kandolf R, Ameis D, Kirschner P, Canu A, Hofschneider PH (1987) In situ detection of enteroviral genomes in myocardial cells by nucleic acid hybridization: an approach to the diagnosis of viral heart disease. Proc Natl Acad Sci USA 84: 6272–6276

  19. 19.

    Kandolf R, Hofschneider PH (1989) Viral heart disease. Springer Semin Immunopathol 11: 1–13

  20. 20.

    Bowles NE, Dubowitz V, Sewry CA, Archard LC (1987) Dermatomyositis, polymyositis and Coxsackie-B-virus infection. Lancet 1: 1004–1007

  21. 21.

    Rose NR, Herskowitz A, Neumann DA, Neu N (1988) Autoimmune myocarditis: a paradigm of post infection autoimmune disease. Immunol Today 9: 117–120

  22. 22.

    Huber SA, Lodge PA (1984) Coxsackievirus B-3 myocarditis in Balb/c mice. Evidence for autoimmunity to myocyte antigens. Am J Pathol 116: 21–29

  23. 23.

    Tarn AC, Smith CP, Spencer KM, Bottazzo GF, Gale EAM (1987) Type 1 (insulin dependent) diabetes: a disease of slow clinical onset? B Med J 294: 342–345

  24. 24.

    Mustonen A, Knip M, Huttunen N-P, Puukka R, Kaar M-L, Åkerblom HK (1984) Evidence of delayed Beta cell destruction in Type 1 (insulin-dependent) diabetic patients with persisting complement-fixing cytoplasmic islet cell antibodies. Diabetologia 27: 421–426

  25. 25.

    Foulis AK (1989) Lawrence lecture. In Type 1 diabetes, does a non-cytopathic viral infection of insulin-secreting B -cells initiate the disease process leading to their autoimmune destruction? Diab Med 6: 666–674

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Foulis, A.K., Farquharson, M.A., Cameron, S.O. et al. A search for the presence of the enteroviral capsid protein VP1 in pancreases of patients with Type 1 (insulin-dependent) diabetes and pancreases and hearts of infants who died of coxsackieviral myocarditis. Diabetologia 33, 290–298 (1990). https://doi.org/10.1007/BF00403323

Download citation

Key words

  • Type 1 (insulin-dependent) diabetes mellitus
  • coxsackie B virus
  • pancreas
  • VP1 capsid protein
  • pancreatitis
  • myocarditis