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. 1978 Oct 1;148(4):1068–1080. doi: 10.1084/jem.148.4.1068

Virus-induced diabetes mellitus. XV. Beta cell damage and insulin- dependent hyperglycemia in mice infected with coxsackie virus B4

PMCID: PMC2185018  PMID: 212506

Abstract

Coxsackie virus B4 that had been passaged in cultures enriched for pancreatic beta cells produced a diabetes-like syndrome when inoculated into SJL/J mice. The infection resulted in insulitis and destruction of beta cells. Viral antigens were found in beta cells by staining with fluorescein-labeled antibody to Coxsackie virus B4. The destruction of beta cells led to a decrease in the immunoreactive insulin content of the pancreas and hypoinsulinemia. The reduction in immunoreactive insulin correlated inversely with the elevation of glucose in the blood and over 80% of the animals were found to be hyperglycemic within 14 days after infection. The percentage of animals with hyperglycemia decreased with time and at the end of 60 days, less than 5% of the animals were still hyperglycemic. However, many of the normoglycemic mice were found to be metabolically abnormal when evaluated by glucose tolerance tests. Studies on the susceptibility of the host showed that only certain inbred strains of mice became diabetic when infected with Coxsackie virus B4. It is concluded that both the passage history of the virus and the strain of the host influence the development of diabetes.

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Selected References

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  1. Boucher D. W., Hayashi K., Rosenthal J., Notkins A. L. Virus-induced diabetes mellitus. III. Influence of the sex and strain of the host. J Infect Dis. 1975 Apr;131(4):462–466. doi: 10.1093/infdis/131.4.462. [DOI] [PubMed] [Google Scholar]
  2. Burch G. E., Tsui C. Y., Harb J. M., Colcolough H. L. Pathologic findings in the pancreas of mice infected with coxsackievirus B4. Arch Intern Med. 1971 Jul;128(1):40–47. [PubMed] [Google Scholar]
  3. Chairez R., Yoon J. W., Notkins A. L. Virus-induced diabetes mellitus. X. Attachment of encephalomyocarditis virus and permissiveness of cultured pancreatic beta cells to infection. Virology. 1978 Apr;85(2):606–611. doi: 10.1016/0042-6822(78)90465-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Coleman T. J., Taylor K. W., Gamble D. R. The development of diabetes following Coxsackie B virus infection in mice. Diabetologia. 1974 Dec;10(6):755–759. doi: 10.1007/BF01219537. [DOI] [PubMed] [Google Scholar]
  5. Craighead J. E. The role of viruses in the pathogenesis of pancreatic disease and diabetes mellitus. Prog Med Virol. 1975;19:161–214. [PubMed] [Google Scholar]
  6. DALLDORF G., GIFFORD R. Adaptation of Group B Coxsackie virus to adult mouse pancreas. J Exp Med. 1952 Nov;96(5):491–497. doi: 10.1084/jem.96.5.491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dippe S. E., Bennett P. H., Miller M., Maynard J. E., Berquist K. R. Lack of causal association between Coxsackie B4 virus infection and diabetes. Lancet. 1975 Jun 14;1(7920):1314–1317. doi: 10.1016/s0140-6736(75)92318-1. [DOI] [PubMed] [Google Scholar]
  8. Gamble D. R., Kinsley M. L., FitzGerald M. G., Bolton R., Taylor K. W. Viral antibodies in diabetes mellitus. Br Med J. 1969 Sep 13;3(5671):627–630. doi: 10.1136/bmj.3.5671.627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gamble D. R., Taylor K. W., Cumming H. Coxsackie viruses and diabetes mellitus. Br Med J. 1973 Nov 3;4(5887):260–262. doi: 10.1136/bmj.4.5887.260. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gamble D. R., Taylor K. W. Seasonal incidence of diabetes mellitus. Br Med J. 1969 Sep 13;3(5671):631–633. doi: 10.1136/bmj.3.5671.631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. HALES C. N., RANDLE P. J. Immunoassay of insulin with insulin-antibody precipitate. Biochem J. 1963 Jul;88:137–146. doi: 10.1042/bj0880137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Harrison A. K., Bauer S. P., Murphy F. A. Viral pancreatitis: ultrastructural pathological effects of Coxsackievirus B3 infection in newborn mouse pancreas. Exp Mol Pathol. 1972 Oct;17(2):206–219. doi: 10.1016/0014-4800(72)90070-6. [DOI] [PubMed] [Google Scholar]
  13. Hierholzer J. C., Farris W. A. Follow-up of children infected in a coxsackievirus B-3 and B-4 outbreak: no evidence of diabetes mellitus. J Infect Dis. 1974 Jun;129(6):741–746. doi: 10.1093/infdis/129.6.741. [DOI] [PubMed] [Google Scholar]
  14. Huff J. C., Hierholzer J. C., Farris W. A. An "outbreak" of juvenile diabetes mellitus: consideration of a viral etiology. Am J Epidemiol. 1974 Oct;100(4):277–287. doi: 10.1093/oxfordjournals.aje.a112036. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lansdown A. B. Pathological changes in the pancreas of mice following infection with Coxsackie B viruses. Br J Exp Pathol. 1976 Jun;57(3):331–338. [PMC free article] [PubMed] [Google Scholar]
  16. Lonberg-Holm K., Crowell R. L., Philipson L. Unrelated animal viruses share receptors. Nature. 1976 Feb 26;259(5545):679–681. doi: 10.1038/259679a0. [DOI] [PubMed] [Google Scholar]
  17. Nelson P. G., Pyke D. A., Gamble D. R. Viruses and the aetiology of diabetes: a study in identical twins. Br Med J. 1975 Nov 1;4(5991):249–251. doi: 10.1136/bmj.4.5991.249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Notkins A. L. Virus-induced diabetes mellitus. Arch Virol. 1977;54(1-2):1–17. doi: 10.1007/BF01314374. [DOI] [PubMed] [Google Scholar]
  19. Onodera T., Jenson A. B., Yoon J. W., Notkins A. L. Virus-induced diabetes mellitus: reovirus infection of pancreatic beta cells in mice. Science. 1978 Aug 11;201(4355):529–531. doi: 10.1126/science.208156. [DOI] [PubMed] [Google Scholar]
  20. Onodera T., Yoon J. W., Brown K. S., Notkina A. L. Evidence for a single locus controlling susceptibility to virus-induced diabetes mellitus. Nature. 1978 Aug 17;274(5672):693–696. doi: 10.1038/274693a0. [DOI] [PubMed] [Google Scholar]
  21. PAPPENHEIMER A. M., KUNZ L. J., RICHARDSON S. Passage of Coxsackie virus (Connecticut-5 strain) in adult mice with production of pancreatic disease. J Exp Med. 1951 Jul 1;94(1):45–64. doi: 10.1084/jem.94.1.45. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Prince G. A., Jenson A. B., Billups L. C., Notkins A. L. Infection of human pancreatic beta cell cultures with mumps virus. Nature. 1978 Jan 12;271(5641):158–161. doi: 10.1038/271158a0. [DOI] [PubMed] [Google Scholar]
  23. Ross M. E., Hayashi K., Notkins A. L. Virus-induced pancreatic disease: alterations in concentration of glucose and amylase in blood. J Infect Dis. 1974 Jun;129(6):669–676. doi: 10.1093/infdis/129.6.669. [DOI] [PubMed] [Google Scholar]
  24. Ross M. E., Notkins A. L. Letter: Coxsackie B viruses and diabetes mellitus. Br Med J. 1974 Apr 27;2(5912):226–226. doi: 10.1136/bmj.2.5912.226. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Ross M. E., Onodera T., Brown K. S., Notkins A. L. Virus-induced diabetes mellitus. IV. Genetic and environmental factors influencing the development of diabetes after infection with the M variant of encephalomyocarditis virus. Diabetes. 1976 Mar;25(3):190–197. doi: 10.2337/diab.25.3.190. [DOI] [PubMed] [Google Scholar]
  26. Tsui C. Y., Burch G. E., Harb J. M. Pancreatitis in mice infected with coxsackievirus B1. Arch Pathol. 1972 May;93(5):379–389. [PubMed] [Google Scholar]
  27. Yoon J. W., Notkins A. L. Virus-induced diabetes mellitus. VI. Genetically determined host differences in the replicating of encephalomyocarditis virus in pancreatic beta cells. J Exp Med. 1976 May 1;143(5):1170–1185. doi: 10.1084/jem.143.5.1170. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Yoon J. W., Onodera T., Jenson A. B., Notkins A. L. Virus-induced diabetes mellitus. XI. Replication of coxsackie B3 virus in human pancreatic beta cell cultures. Diabetes. 1978 Jul;27(7):778–781. doi: 10.2337/diab.27.7.778. [DOI] [PubMed] [Google Scholar]
  29. Yoon J., Onodera T., Notkins A. L. Virus-induced diabetes mellitus: VIII. Passage of encephalomyocarditis virus and severity of diabetes in susceptible and resistant strains of mice. J Gen Virol. 1977 Nov;37(2):225–232. doi: 10.1099/0022-1317-37-2-225. [DOI] [PubMed] [Google Scholar]

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