1887

Abstract

The development of diabetes in mice induced by encephalomyocarditis (EMC) virus provides the best experimental evidence that viruses have an aetiological role in the pathogenesis of this disease. The major capsid protein (VP1) of EMC virus is important for both the attachment of the virus to pancreatic beta cells and for the determination of antigenicity. This experiment was initiated to clone the gene for the major capsid protein, VP1, of the diabetogenic EMC (EMC-D) virus, express the VP1 protein, and test whether the recombinant VP1 protein can prevent development of EMC-D virus-induced diabetes in mice. We successfully cloned the VP1 gene of the EMC-D virus in the expression vector pRSET and subsequently expressed the protein in . The recombinant VP1 protein was then purified by affinity chromatography. Five- to six-week-old male SJL/J mice were immunized intraperitoneally with purified VP1 protein and then challenged after various intervals with highly diabetogenic EMC-D virus. None of the VP1-immunized mice developed diabetes, irrespective of the interval between immunization and virus challenge, whereas 80 to 95% of the EMC-D virus-infected control mice did develop diabetes. All of the VP1-immunized mice showed intact pancreatic islet architecture, whereas most of the infected control mice showed severe beta cell necrosis and lymphocytic infiltration of their pancreatic islets. On the basis of these observations, we conclude that the recombinant VP1 protein of EMC-D virus can completely prevent the development of EMC-D virus-induced diabetes in mice.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-76-10-2557
1995-10-01
2021-10-25
Loading full text...

Full text loading...

/deliver/fulltext/jgv/76/10/JV0760102557.html?itemId=/content/journal/jgv/10.1099/0022-1317-76-10-2557&mimeType=html&fmt=ahah

References

  1. Ahmad N., Abraham A. A. 1982; Pancreatic islets with Coxsackie virus B5 infection. Human Pathology 13:661–662
    [Google Scholar]
  2. Arnon R. 1991; Synthetic peptides as the basis for vaccine design. Molecular Immunology 28:209–215
    [Google Scholar]
  3. Asplin C. M., Cooney M. K., Crossley J. R., Dornan T. L., Raghu P., Palmer J. P. 1982; Coxsackie B4 infection and islet cell antibodies three years before overt diabetes. Journal of Pediatrics 101:398–400
    [Google Scholar]
  4. Bae Y. S., Yoon J. W. 1993; Determination of diabetogenicity attributable to a single amino acid, Ala-776, on the polyprotein of encephalomyocarditis virus. Diabetes 42:435–443
    [Google Scholar]
  5. Baek H. S., Yoon J. W. 1990; Role of macrophages in the pathogenesis of encephalomyocarditis virus-induced diabetes in mice. Journal of Virology 64:5708–5715
    [Google Scholar]
  6. Champsaur H., Bottazzo G., Bertrams J., Assan R., Bach C. 1982; Virologic, immunologic and genetic factors in insulin-dependent diabetes mellitus. Journal of Pediatrics 100:15–20
    [Google Scholar]
  7. Coleman T. J., Gamble D. R., Taylor K. W. 1973; Diabetes in mice after Coxsackie B4 virus infection. British Medical Journal 3:25–27
    [Google Scholar]
  8. Coleman T. J., Taylor K. W., Gamble D. R. 1974; The development of diabetes following Coxsackie B virus infection in mice. Diabetologia 10:755–759
    [Google Scholar]
  9. Craighead J. E. 1975; The role of viruses in the pathogenesis of pancreatic diseases and diabetes mellitus. Progress in Medical Virology 19:161–214
    [Google Scholar]
  10. Craighead J. E., McLane M. F. 1968; Diabetes mellitus; induction in mice by encephalomyocarditis virus. Science 162:913–914
    [Google Scholar]
  11. Davoren P. R. 1962; The isolation of insulin from a single cat pancreas. Biochimica et Biophysica Acta 63:150–153
    [Google Scholar]
  12. Eun H. M., Bae Y. S., Yoon J. W. 1988; Amino acid deferences in capsid protein, VP1, between diabetogenic and nondiabetogenic variants of encephalomyocarditis virus. Virology 163:369–373
    [Google Scholar]
  13. Gladisch R., Hoffmann W., Waldherr R. 1976; Myocarditis and insulitis in Coxsackie virus infection. Zeitschrift fur Kardiologie 65:837–849
    [Google Scholar]
  14. Hales C. N., Randle P. J. 1963; Immunoassay of insulin with insulin antibody precipitate. Biochemical Journal 88:137–146
    [Google Scholar]
  15. Homa F. L., Brideau R. J., Lehmann D. J., Thomsen D. R., Olmsted R. A., Wathen M. W. 1993; Development of a novel subunit vaccine that protects cotton rats against both human respiratory syncytial virus and human parainfluenza virus type 3. Journal of General Virology 74:1995–1999
    [Google Scholar]
  16. Jenson A., Rosenbert H., Notkins A. L. 1980; Pancreatic islet cell damage in children with fatal viral infections. Lancet ii:354–358
    [Google Scholar]
  17. Kang Y., Yoon J. W. 1993; A genetically determined host factor controlling susceptibility to EMC virus-induced diabetes in mice. Journal of General Virology 74:1207–1213
    [Google Scholar]
  18. Ko I. Y., Ihm S. H., Yoon J. W. 1991; Studies on autoimmunity for initiation of beta cell destruction. VIII. Pancreatic beta cell dependent autoantibody to a 38 kilodalton protein precedes the clinical onset of diabetes in BB rats. Diabetologia 34:548–554
    [Google Scholar]
  19. Kroll D. J., Abdel-Malek-Abdel-Hafiz H., Marcell T., Simpson S., Chen C. Y., Gutierrez-Hartmann A., Lustbader J. W., Hoeffler J. P. 1993; A multifunctional prokaryotic protein expression system: overproduction, affinity purification, and selective detection. DNA and Cell Biology 12:441–453
    [Google Scholar]
  20. Nigro G., Pacella M. E., Patane E., Misulla M. 1986; Multisystem Coxsackie virus B6 infection with findings suggestive of diabetes mellitus. European Journal of Paediatrics 145:557–559
    [Google Scholar]
  21. Niklasson B. S., Dobersen M. J., Peters C. J., Ennis W. H., Moller E. 1985; An outbreak of Coxsackie virus B infection followed by one case of diabetes mellitus. Scandinavian Journal of Infectious Diseases 17:15–18
    [Google Scholar]
  22. Notkins A. L., Yoon J. W. 1983; Virus-induced diabetes in mice prevented by a live attenuated vaccine. New England Journal of Medicine 306:486
    [Google Scholar]
  23. Notkins A. L., Yoon J. W., Onodera T., Jenson A. B. 1981; Virus-induced diabetes. Perspectives in Virology XI:141–162
    [Google Scholar]
  24. Orchard T. J., Becker A. J., Atchison R. W., Laporte R. E., Wagener D. K., Rabin B. S., Kuller L. H., Drash A. L. 1982; The development of type 1 (insulin-dependent) diabetes mellitus: two contrasting presentations. Diabetologia 25:89–92
    [Google Scholar]
  25. Palmer J. P., Cooney M. K., Croddley J. R., Hollander P. H., Asplin C. M. 1981; Antibodies to viruses and to pancreatic islets in nondiabetic and insulin-dependent diabetic patients. Diabetes Care 4:525–528
    [Google Scholar]
  26. Ross M. E., Onodera T., Brown K. S., Notkins A. L. 1976; Virus-induced diabetes mellitus IV. Genetic and environmental factors influencing the development of diabetes after infection with the M variant of encephalomyocarditis virus. Diabetes 25:190–197
    [Google Scholar]
  27. Rossini A. A., Greiner D. L., Friedman H. P., Mordes J. P. 1993; Immunopathogenesis of diabetes mellitus. Diabetes Review 1:43–75
    [Google Scholar]
  28. Scott F. W., Marliss E. B. 1991; Conference summary: Diet as an environmental factor in development of insulin-dependent diabetes mellitus. Canadian Journal of Physiology and Pharmacology 69:311–319
    [Google Scholar]
  29. Studier F. W., Rosenbert A. H., Dunn J. J., Dubendorgg J. W. 1990; Use of T7 RNA polymerase to direct expression of cloned genes. Methods in Enzymologv 185:60–89
    [Google Scholar]
  30. Todd J. A., Bain S. C. 1992; A practical approach to identification of susceptibility genes for IDDM. Diabetes 41:1029–1034
    [Google Scholar]
  31. Toniolo A., Onodera T., Jordan G., Yoon J. W., Notkins A. L. 1982; Virus-induced diabetes mellitus: glucose abnormalities produced in mice by all six members of the Coxsackie B virus group. Diabetes 31:496–499
    [Google Scholar]
  32. Wilson C., Connolly J. M., Thomson D. 1977; Coxsackie B2 virus infection and acute onset diabetes in a child. British Medical Journal 1:1008
    [Google Scholar]
  33. Yoon J. W. 1990; Role of viruses and environmental factors in the induction of diabetes. Current Topics in Microbiology and Immunology 164:95–123
    [Google Scholar]
  34. Yoon J. W., Kominek H. 1995; Role of Coxsackie B viruses in the pathogenesis of diabetes mellitus. In Microbial Infections and Pathogenesis Edited by Rose N. R., Friedman H. New York: Plenum Press; (in press)
    [Google Scholar]
  35. Yoon J. W., Notkins A. L. 1976; Virus-induced diabetes mellitus. VI. Genetically determined host differences in the replication of encephalomyocarditis virus in pancreatic beta cells. Journal of Experimental Medicine 143:1170–1185
    [Google Scholar]
  36. Yoon J. W., Park Y. H. 1993; Viruses as triggering agents of insulin-dependent diabetes mellitus. In Causes of Diabetes pp 83–103 Edited by Leslie R. D. G. New York: John Wiley and Sons;
    [Google Scholar]
  37. Yoon J. W., Lesniak M. A., Fussganger R., Notkins A. L. 1976; Genetic differences in susceptibility of pancreatic beta cells to virus-induced diabetes. Nature 264:178–180
    [Google Scholar]
  38. Yoon J. W., Onodera T., Notkins A. L. 1977; Virus-induced diabetes mellitus. VIII. Passage of encephalomyocarditis virus and severity of diabetes in susceptible and resistant strains of mice. Journal of General Virology 37:225–232
    [Google Scholar]
  39. Yoon J. W., Onodera T., Notkins A. L. 1978; Virus-induced diabetes mellitus XV: beta cell damage and insulin-dependent hyperglycaemia in mice infected with Coxsackie virus B4. Journal of Experimental Medicine 148:1068–1080
    [Google Scholar]
  40. Yoon J. W., Austin M., Onodera T., Notkins A. L. 1979; Virus-induced diabetes mellitus: isolation of a virus from the pancreas of a child with diabetic ketoacidosis. New England Journal of Medicine 300:1173–1179
    [Google Scholar]
  41. Yoon J. W., McClintock P. R., Onodera T., Notkins A. L. 1980; Virus-induced diabetes mellitus. XVIII. Inhibition by a nondiabetogenic variant of encephalomyocarditis virus. Journal of Experimental Medicine 152:878–892
    [Google Scholar]
  42. Yoon J. W., Morishima T., McClintock P. R., Austin M., Notkins A. L. 1984; Virus-induced diabetes mellitus: mengovirus infects pancreatic beta cells in strains of mice resistant to the diabetogenic effect of encephalomyocarditis virus. Journal of Virology 50:684–690
    [Google Scholar]
  43. Yoon J. W., London W., Curfman B., Brown R., Notkins A. L. 1986; Coxsackie virus B4 produces transient diabetes in nonhuman primates. Diabetes 35:712–716
    [Google Scholar]
  44. Yoon J. W., Wong A. K. C., Bae Y. S., Eun H. M. 1988a; An apparent deletion of an oligonucleotide detected by RNA fingerprint in the nondiabetogenic B variant of encephalomyocarditis virus is caused by a point mutation. Journal of Virology 62:637–644
    [Google Scholar]
  45. Yoon J. W., Ko W., Bae Y. S., Pak C. Y., Amano K., Eun H. M., Kim M. K. 1988b; Identification of antigenic differences between the diabetogenic and nondiabetogenic variants of encephalomyocarditis virus using monoclonal antibodies. Journal of General Virology 69:1085–1090
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-76-10-2557
Loading
/content/journal/jgv/10.1099/0022-1317-76-10-2557
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error