Virus and Insulin-Dependent Diabetes Mellitus

  • S. A. Huber
  • B. R. MacPherson


The theory that viruses cause insulin-dependent diabetes mellitus (IDDM) has been advanced sporadically for more than a century. During the past decade this theory has attracted renewed interest following the description by Craighead and McLane (1968) of a murine model of IDDM induced by the M variant of encephalomyocarditis (EMC) virus. An intriguing aspect of this model, which recapitulates many of the metabolic and pathologic features of human IDDM, is that EMC viruses are picomaviruses closely related to certain human pathogens, specifically coxsackieviruses. Although there is little evidence to suggest that EMC viruses per se cause human diabetes, efforts to incriminate Coxsackieviruses in IDDM have met with considerable success. In this chapter, we will review the evidence linking viruses to the etiology of IDDM.


Beta Cell Rubella Virus Islet Cell Antibody Mumps Virus Encephalomyocarditis Virus 


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  1. Adams, S. F., 1926, The seasonal variation in the onset of acute diabetes: The age and sex factors in 1000 diabetic patients, Arch. Intern Med., 37: 861–864.CrossRefGoogle Scholar
  2. Adi, F. C., 1974, Diabetes mellitus associated with epidemic of infectious hepatitis in Nigeria, Br. Med. J. 1: 183–185.PubMedCrossRefGoogle Scholar
  3. Alford, Jr., C. A., 1976, Rubella, in: Infectious Diseases of the Fetus and Newborn Infant ( J. S. Remington and J. O. Klein, eds.), pp. 71–106, W. B. Saunders, Philadelphia.Google Scholar
  4. Barbieri, V., 1909, Pancreatite subacuta e glicosuria secondairie a parotite epeidemica, Gaz Osped. 30: 273, 1909.Google Scholar
  5. Barboni, E., and Manocchi, I., 1962, Alterazionia pancreatiche in bovini con diabete mellito post-aftoso, Arch. Vet. Ital. 13: 477–489.Google Scholar
  6. Barbosa, J., King, R., and Noreen, H. 1977, The histocompatibility system in juvenile, insulin-dependent diabetic multiplex kindreds, J. Clin. Invest. 60: 989–998.PubMedCrossRefGoogle Scholar
  7. Battazzo, G. F., Florin Christensen, A., and Doniach, A., 1974, Islet cell antibodies in diabetes mellitus with autoimmune polyendocrine deficiencies, Lancet 2: 1279–1283.CrossRefGoogle Scholar
  8. Baum, S. G. and Litman, M., 1979, Mumps virus, in: Principles and Practice of Infectious Diseases ( G. L.Mandell, R. G. Douglas, and J. E. Bennett, eds.), pp. 1176–1185, John Wiley, New York.Google Scholar
  9. Block, M. B., Berk, J. E., Fridhandler, L. S., Steiner, D. F., and Rubenstein, A. H., 1973, Diabetic ketoacidosis associated with mumps virus infection, Ann. Intern. Med. 78: 663–667.PubMedGoogle Scholar
  10. Bloom, A., Hayes, T. M., and Gamble, D. R., 1975, Register of newly diagnosed diabetic children, Br.Med. J. 3: 580–583.PubMedCrossRefGoogle Scholar
  11. Bostrom, K., 1968, Pathoanatomical findings in a case of mumps with pancreatis, myocarditis, orchitis, epididymitis, and seminal vesiculitis, Virchows Arch. Pathol. Anat. 344: 111–117.CrossRefGoogle Scholar
  12. Boucher, D. W., Hayashi, K., Rosenthal, J., and Notkins, A. L., 1975, Virus induced diabetes mellitus. III. Influence of sex and strain of the host, J. Infect. Dis. 131: 462–466.PubMedCrossRefGoogle Scholar
  13. Bunnell, C. E., and Monif, G. R. G., 1972, Interstitial pancreatitis in the congenital rubella syndrome, J. Pediatr. 80: 465–466.PubMedCrossRefGoogle Scholar
  14. Burgess, J. A., Kirkpatrick, K. L., and Menser, M. A., 1974, Fulminant onset of diabetes mellitus during an attack of infectious mononucleosis, Med. J. Aust. 2: 706–707.PubMedGoogle Scholar
  15. Burch, G. E., Tsui, C-Y, Harb, J. M., and Colcolough, H. L., 1971, Pathologic findings in the pancreas of mice infected with coxsackievirus B4, Arch. Intern. Med. 128: 40–47.PubMedCrossRefGoogle Scholar
  16. Buschard, K., Rygaard, J., and Lund, E., 1976, The inability of diabetogenic virus to induce diabetes mellitus in athymic (nude) mice, Acta Pathol. Microbiol. Scand.[C] 84: 299–303.Google Scholar
  17. Centers for Disease Control, 1980, Mumps vaccine: Recommendation of the Immunization Practices Advisory Committee, Ann. Intern. Med. 92: 803–804.Google Scholar
  18. Chairez, R., Yoon, J.-W. and Notkins, A. L., 1978, Virus-induced diabetes mellitus. X. Attachment of encephalomyocarditis virus and permissiveness of cultured pancreatic B cells to infection, Virology, 85: 606–611.PubMedCrossRefGoogle Scholar
  19. Champsaur, H., Dussaux, E., Samolyk, D., Fabre, M., Bach, C. H., and Assan, R., 1980, Diabetes and coxsackie virus B5 infection, Lancet 1: 251.PubMedCrossRefGoogle Scholar
  20. Christau, B., Dromann, H., and Andersen, O. 0., 1977, Incidence, seasonal, and geographical patterns of juvenile onset, insulin-dependent diabetes in Denmark, Diabetologia, 13: 281–284.Google Scholar
  21. Cole, L., 1933, Pancreatitis in mumps, Br. Med. J. 1: 1080.CrossRefGoogle Scholar
  22. Cole, L., 1934, Diabetes mellitus in children, Lancet 1: 947950.CrossRefGoogle Scholar
  23. Cooper, L. Z., 1975, Infections of the Fetus and Newborn Infant, Alan R. Liss, New York.Google Scholar
  24. Craighead, J. E., 1966, Pathogenicity of the M and E variants of the encephalomyocarditis (EMC) virus. II. Lesions of the pancreas, parotid and lacrimal glands, Am. J. Pathol. 48: 375386.Google Scholar
  25. Craighead, J. E., and McLane, M. F. B., 1968, Diabetes mellitus. Induction in mice by encephalomyocarditis virus, Science 162: 913–914.PubMedCrossRefGoogle Scholar
  26. Craighead, J. E., and Steinke, J., 1971, Diabetes mellitus-like syndrome in mice infected with encephalomyocarditis virus, Am. J. Pathol. 63: 119–134.PubMedGoogle Scholar
  27. Craighead, J. E. and Higgins, D. A., 1974, Genetic influences affecting the occurrence of a diabetes mellitus like disease in mice infected with the encephalomyocarditis virus, Jr. Exp. Med., 139: 414–426.CrossRefGoogle Scholar
  28. Craighead, J. E., 1975, The role of viruses in the pathogenesis of pancreatic disease and diabetes mellitus, Prog. Med. Virol. 19: 161–214.PubMedGoogle Scholar
  29. Cudworth, A. G., and Woodrow, J. C., 1975a, Evidence for HL-A-linked genes in “juvenile” diabetes mellitus, Br. Med. J. 3: 133–135.PubMedCrossRefGoogle Scholar
  30. Cudworth, A. G., and Woodrow, J. C., 1975b, HLA system and diabetes mellitus, Diabetes 24: 345–349.PubMedCrossRefGoogle Scholar
  31. Cudworth, A. G., White, G. B. B., Woodrow, J. C., Gambel, D. R., Lendrum, R., and Bloom, A., 1977, A etiology of juvenile-onset diabetes. A prospective study, Lancet, 1: 385–388.PubMedCrossRefGoogle Scholar
  32. Curren, E. C., 1979, Enterovirus infections, in: Textbook of Pediatrics ( W. E. Nelson, V. C. Vaughan III, R. J. McKay Jr., and R. E. Behmnan, eds.), pp. 914–926, W. B. Saunders, Philadelphia.Google Scholar
  33. Dacou-Voutetakis, C. D., Constantinidis, M., and Moschos, A., 1974, Diabetes mellitus following mumps, Am. J. Dis. Child. 127: 890–891.PubMedGoogle Scholar
  34. DaFoe, D. C., Naji, A., Plotkin, S. A., and Barker, C. F., 1980, Susceptibility to diabetogenic virus: Host versus pancreatic factors, J. Surg. Res. 28: 338–347.PubMedCrossRefGoogle Scholar
  35. Daldorf, G., 1950, Coxackie viruses, Bull. N. Y. Acad. Med. 26: 329–335.Google Scholar
  36. D’Andrea, B. J., Wilson, G. L., and Craighead, J. E., 1981, Effect of genetic obesity in mice on the induction of diabetes by encephalomyocarditis virus, Diabetes 30: 451–454.PubMedCrossRefGoogle Scholar
  37. Dick, J. S., 1934, Pancreatitis in mumps, Br. Med. J. 2: 35.CrossRefGoogle Scholar
  38. Di Pietro, C., Del Guercia, M. J., Paolino, G. P., Barbi, M., Ferrante, P., and Chiumello, G., 1979, Type I diabetes and coxsackie virus infection, Heiv. Paediatr. Acta 34: 557–561.Google Scholar
  39. Dippe, S. E., Miller, M., Bennett, P. H., and Maynard, J. E., 1975, Lack of causal association between coxsackie B-4 virus infection and diabetes, Lancet 1: 1314–1317.PubMedCrossRefGoogle Scholar
  40. Doberson, M. J., Scharff, J. E., Ginsberg-Fellner, F., and Notkins, A. L., 1980, Cytotoxic autoantibodies to beta cells in the serum of patients with insulin-dependent diabetes mellitus, N. Engl. J. Med. 303: 1493–1498.CrossRefGoogle Scholar
  41. El-Hagrassy, M. M. O., and Banatvala, J. E., 1980, Coxsackie B-virus specific IgM responses in patients with cardiac and other diseases, Lancet 2: 1160–1162.PubMedCrossRefGoogle Scholar
  42. Evans, R. and Alexander, P. L., 1971, Rendering macrophages specifically cytotoxic by a factor released by immune lymphoid cells, Transplantation 12: 227–229.PubMedCrossRefGoogle Scholar
  43. Farnam, L. W., 1922, Pancreatitis following mumps: Report of a case with operation, Am. J. Med. Sci. 163: 859–870.Google Scholar
  44. Fidler, I. J., 1975, Activation in vitro of mouse macrophages by syngeneic, allogeneic, or xenogeneic lymphocyte supematants, J. Natl. Cancer Inst. 55: 1159–1163.PubMedGoogle Scholar
  45. Floret, D., Rosenberg, D., Hage, G. N., and Monnet, P., 1980, Hyperthyroidism, diabetes mellitus, and the congenital rubella syndrome, Acta Paediatr. Scand., 69: 259–261.PubMedCrossRefGoogle Scholar
  46. Forrest, J. M., Menser, M. A., and Harley, S. S, 1969, Diabetes mellitus and congenital rubella, Pediatrics, 44: 445–446.PubMedGoogle Scholar
  47. Forrest, J. M., Menser, M. A., and Burgess, J. A. 1971, High frequency of diabetes mellitus young adults with congenital rubella, Lancet 2: 332–334.PubMedCrossRefGoogle Scholar
  48. Freeman, A. G., 1962, Mumps followed by diabetes Lancet 2:96.Google Scholar
  49. Freeman, B. A., 1979 Textbook of MicrobiologyW. B. Saunders, Philadelphia.Google Scholar
  50. Gamble, D. R., 1980a, Relation of antecedent illness to development of diabetes in children, Br. Med. J. 281: 99–101.PubMedCrossRefGoogle Scholar
  51. Gamble, D. R., 1980b, The epidemiology of insulin dependent diabetes with reference to the relationship of virus infection to its etiology, Epidemiol. Rev., 2: 49–70.PubMedGoogle Scholar
  52. Gamble, D. R., and Taylor, K. W., 1969, Seasonal incidence of diabetes mellitus, Br. Med. J., 3: 631–633.PubMedCrossRefGoogle Scholar
  53. Gamble, D. R., Kinsley, M. L., Fitzgerald, M. G., Bolton, R., and Taylor, D. W., 1969, Viral antibodies in diabetes mellitus, Br. Med. J. 3: 627–630.CrossRefGoogle Scholar
  54. Gamble, D. R., Taylor, K. W., and Cumming, H., 1973, Coxsackie viruses and diabetes mellitus, Br. Med. J. 4: 260–262.PubMedCrossRefGoogle Scholar
  55. Garavoy, M. R., Barbosa, J., Reddish, M., Martin, S., Norcen, H., Yunis, E. J., and Carpenter, C. B., 1978, HLA-DR antigens and unique serological reactions in juvenile-onset diabetes mellitus, Transplant Proc. 10: 967–969.Google Scholar
  56. Gepts, W., 1965, Pathologic anatomy of the pancreas in juvenile diabetes mellitus, Diabetes 14: 619–633.PubMedGoogle Scholar
  57. Gepts, W., and DeMey, J., 1978, Islet cell survival determined by morphology. An immunocytochemical study of the islets of Langerhans in juvenile diabetes mellitus, Diabetes 27: 251–261.PubMedGoogle Scholar
  58. Gilhespy, F. B., and Holden, H. S., 1917, Grave diabetes mellitus with pulmonary tuberculosis following mumps Br. Med. J.2:115.Google Scholar
  59. Ginsberg, H. S., 1969, Picornaviruses, in: Microbiology ( Davis, B. D., Dulbecco, R., Eisen, H. N.,Ginsberg, H. S., and Wood, W. B., eds.), pp. 1095–1118, Harper and Row, New York.Google Scholar
  60. Ginsberg, H. S., and Dulbecco, R., 1980, Multiplication and genetics of animal viruses, in: Microbiology,3rd edition (Davis, B. D., Dulbecco, R., Eisen, H. N., and Ginsberg, H. S., eds.), pp. 967–999, Harper and Row, Hagerstown, MD.Google Scholar
  61. Glasgow, L. A., and Overall Jr., J. C., 1979, Infections, in: Textbook of Pediatrics ( W. E. Nelson, V. C. Vaughan III, R. J. McKay Jr., and R. G. Behrman, eds.), pp. 483–485, W. B. Saunders, Philadelphia.Google Scholar
  62. Gorsuch, A. N., Lister, J., Dean, B. M., Spencer, K. M., McNally, J. M., and Bottazzo, G. F., 1981, Evidence for along prediabetic period in type I (insulin-dependent) diabetes mellitus, Lancet 1: 1363–1365.CrossRefGoogle Scholar
  63. Gundersen, E., 1927, Is diabetes of infectious origin?, J. Infec. Dis., 41: 197–202.CrossRefGoogle Scholar
  64. Halvorson, E. P., 1977, Diabetes mellitus and congenital rubella: Report of a case, Mt. Sinai J. Med. 44: 566–567.PubMedGoogle Scholar
  65. Handwerger, B. S., Fernandes, G., and Brown, D. M., 1980, Immune and autoimmune aspects of diabetes mellitus, Hum. Pathol. 11: 338–352.PubMedCrossRefGoogle Scholar
  66. Harris, H. F., 1899, A case of diabetes mellitus quickly following mumps, Boston Med. Surg. J. 140: 465–469.CrossRefGoogle Scholar
  67. Hay, D. R., 1949, Studies in preventive hygiene from the Otago Medical School. I. The relation of maternal rubella to congenital deafness and other abnormalities in New Zealand, N.Z. Med. J. 48:604–608. Helmke, K., Otten, A., and Willerus, W., 1980, Islet cell antibodies in children with mumps infection, Lancet 2: 211–212.Google Scholar
  68. Henle, G., Henle, W., Wendell, K. K., and Rosenberg, P., 1948, Isolation of mumps virus from human beings with induced apparent or inapparent infections, J. Exp. Med. 88: 223–232.PubMedCrossRefGoogle Scholar
  69. Hierholzer, J. C., and Farris, W. A., 1974, Follow-up of children infected in a Coxsackievirus B-3 and B-4 outbreak: No evidence of diabetes mellitus, J. Infect. Dis., 129: 741–746.PubMedCrossRefGoogle Scholar
  70. Hinden, E., 1962, Mumps followed by diabetes, Lancet 1: 1381.PubMedCrossRefGoogle Scholar
  71. Huang, S. -W., and Maclaren, N. K., 1976, Insulin-dependent diabetes: A disease of autoaggression, Science, 192: 64–66.PubMedCrossRefGoogle Scholar
  72. Huber, S. A., Job, L. P., and Woodruff, J. F., 1980, Lysis of infected myofibers by Coxsackievirus B-3-immune T lymphocytes, Am. J. Pathol. 98: 681–694.PubMedGoogle Scholar
  73. Huber, S. A., Job, L. P., and Woodruff, J. F., 1981, Sex-related differences in the pattern of Coxsackievirus B-3-induced immune spleen cell cytotoxicity against virus-infected myofibers, Infect. Immun. 32: 68–73.PubMedGoogle Scholar
  74. Huff, J. C., Hierholzer, J. D., and Farris, W. A., 1974, An `outbreak“ of juvenile diabetes mellitus: Consideration of a viral etiology, Am. J. Epidemiol. 100: 277–287.PubMedGoogle Scholar
  75. Hulquist, G., Nordvall, S., and Sundstrom, C., 1973, Insulitis in cytomegalovirus infection in a newborn infant, Ups. J. Med. Sci. 78: 139–144.CrossRefGoogle Scholar
  76. Irvine, W. J., Clark, B. F., Scarth, L., Cullen, D. R., and Duncan, L. J. P., 1970, Thyroid and gastric autoimmunity in patients with diabetes mellitus, Lancet 2: 163–168.PubMedCrossRefGoogle Scholar
  77. Jansen, F. K., Muntefering, H., and Schmidt, W. A. K., 1977, Virus induced diabetes mellitus and the immune system. I. Suggestion that appearance of diabetes depends on immune reactions, Diabetologia 13: 545–549.PubMedCrossRefGoogle Scholar
  78. Jansen, F. K., Thurnerssen, O., and Muntefering, H., 1979, Virus induced diabetes and the immune system. II. Evidence for an immune pathogenesis of the acute phase of diabetes, Biomedicine 31: 1–2.PubMedGoogle Scholar
  79. Jenson, A. B., Rosenberg, H. S., and Notkins, A. L., 1980, Pancreatic islet cell damage in children with fatal virus infections, Lancet 2: 354–358.PubMedGoogle Scholar
  80. John, H. J., 1934, The diabetic child: Etiologic factors, Ann. Intern. Med. 8:198–213. John, H. J., 1949, Diabetes mellitus in children, J. Pediatr. 35: 723–744.Google Scholar
  81. Johnson, G. M., and Tudor, R. B., 1980, Diabetes mellitus and congenital rubella infection, Am. J. Dis. Child. 120: 453–455.Google Scholar
  82. Joklik, W. K., 1980, The virus multiplication cycle, in: Zinsser Microbiology ( W. K. Joklik, H. Willet, and D. B. Amos, eds.), pp. 1040–1086, Appleton-Century-Crofts, New York.Google Scholar
  83. Junker, K., Egeberg, J., Kromann, H., 1977, An autopsy study of the islets of Langerhans in acute-onset juvenile diabetes mellitus, Acta Pathol. Microbiol. Scand. [A] 85: 699–706.Google Scholar
  84. Kahana, D., and Brant, M., 1967, Diabetes in an infant following inapparent mumps. Clin. Pediatr. 6: 124–125.CrossRefGoogle Scholar
  85. Kim, Y. B., Huh, N. D., Koren, H. S., and Amos, D. B., 1980, Natural killing (NK) and antibody-dependent cellular cytotoxicity (ADCC) in specific pathogen-free (SPF) miniature swine and germ free piglets. I. Comparison of NK and ADCC, J. Immunol. 125: 753–762.Google Scholar
  86. King, R. C., 1962, Mumps followed by diabetes, Lancet 2: 1055.CrossRefGoogle Scholar
  87. Kremer, H. U., 1947, Juvenile diabetes as a sequel to mumps, Am. J. Med. 3:257–258. LeCompte, P. M., 1958, “Insulitis” in early juvenile diabetes, Arch. Pathol., 66: 450–457.Google Scholar
  88. LeCompte, P. M., and Gepts, W., 1977, The pathology of juvenile diabetes, in: The Diabetic Pancreas (B.W. Volk, and K. F. Weltmann, eds.), pp. 325–364, Plenum Press, New York.Google Scholar
  89. Lemoine, L. G. H., and Lapassat, M. F., 1903, Un cas de pancreatite ourlienne avec autopsie, Bull. Soc. Med. Hop., Paris 24: 640–647.Google Scholar
  90. Lerner, A. M., Wilson, F. M., and Reyes, M. P., 1975, Enteroviruses and the heart (with special emphasis upon the probable role of Coxsackieviruses, group B, types 1–5). I. Epidemiological and experimental studies, Mod. Concepts Cardiovasc. Dis. 44: 7–10.PubMedGoogle Scholar
  91. Lernmark, A., Freedman, Z. R., Hofmann, C., Rubenstein, A. H., Steiner, D. F., Jackson, R. L., Winter, R. J., and Traisman, H. S., 1978, Islet cell surface antibodies in juvenile diabetes mellitus, N. Engl. J. Med. 299: 375–380.PubMedCrossRefGoogle Scholar
  92. Limper, M. A., and Miller, A. J., 1935, Diabetes mellitus with extensive gangrene in early infancy, Am. J. Dis. Child. 50: 1216–1230.Google Scholar
  93. Madden, D. L., Fuccillo, D. A., Traub, R. G., Ley, A. C., Sever, J. L., and Beadle, E. L., 1978, Juvenile onset diabetes mellitus in pregnant women: Failure to associate with Coxsackie B1–6, mumps or respiratory syncytial virus infections, J. Pediatr. 92: 959–960.PubMedCrossRefGoogle Scholar
  94. Marcy, S. M., and Kibrick, S., 1977, Mumps, in: Infectious Diseases, 2nd ed., ( P. D. Hoeprich, ed.), pp. 621–627, Harper and Row, Hagerstown, MD.Google Scholar
  95. McCrae, W. M., 1963, Diabetes mellitus following mumps, Lancet 1: 1300–1301.CrossRefGoogle Scholar
  96. McMichael, A. J., 1978, HLA restriction of human cytotoxic T lymphocytes specific for influenza virus: Poor recognition of virus associated with HLA AZ, J. Exp. Med. 148: 1458–1467.PubMedCrossRefGoogle Scholar
  97. Melin, K., and Ursing, B., 1958, Diabetes mellitus som komplikation till parotitis epidemica, Nord. Med. 60: 1715–1716.PubMedGoogle Scholar
  98. Menser, M. A., Dods, L., and Harley, J. D., 1967, A twenty-five year follow-up of congenital rubella, Lancet 2: 1347–1350.PubMedCrossRefGoogle Scholar
  99. Menser, M. A., Forrest, J. M., and Honeyman, M. C., 1974, Diabetes, HLA antigens and congenital rubella, Lancet 2: 1508–1509.Google Scholar
  100. Messaritakis, J., Karabula, C., Kattamis, C., and Matsemiotis, N., 1971, Diabetes following mumps in sibs, Arch. Dis. Child. 46: 561–562, 1971.PubMedCrossRefGoogle Scholar
  101. Nelson, P. G., Pyke, D. A., Cudworth, A. G., Woodrow, J. C., Batchelor, J. R., 1975a, Histocompatibility antigens in diabetic identical twins, Lancet 2: 193–194.PubMedCrossRefGoogle Scholar
  102. Nelson, P. G., Pyke, D. A., and Gamble, D. R., 1975b, Viruses and the etiology of diabetes: A study in identical twins, Br. Med. J. 4: 249–251.PubMedCrossRefGoogle Scholar
  103. Nerup, J., and Binder, C., 1973, Thyroid, gastric and adrenal autoimmunity in diabetes mellitus, Acta Endocrinol. 72: 279–286.PubMedGoogle Scholar
  104. Nerup, J., Platz, P., Anderson, O. O., Christy, M., Lyngsoe, J., Poulson, J. E., Ryder, L. P., Thomsen, M., Staub Nielsen, L. S., and Svejgaard, A., 1974, HL-A antigens and diabetes mellitus, Lancet 2: 864–866, 1974.PubMedCrossRefGoogle Scholar
  105. Onodera, T., Jenson, A. B., Yoon, J. W., and Notkins, A. L., 1978, Virus induced diabetes mellitus. Reovirus infection of pancreatic B cells in mice, Science 201: 529–531.PubMedCrossRefGoogle Scholar
  106. Paque, R. E., Gauntt, C. J., Nealon, T. J., and Trousdale, M. P., 1978, Assessment of cell mediated hypersensitivity against Coxsackie virus B3 viral-induced myocarditis utilizing hypertonic extracts of cardiac tissue, J. Immunol. 120: 1672–1678.PubMedGoogle Scholar
  107. Patrick, A., 1924, Acute diabetes following mumps, Br. Med. J. 2: 802.PubMedCrossRefGoogle Scholar
  108. Patterson, K., Chandra, R. S., and Bennett Jenson, A., 1981, Congenital rubella, insulitis, and diabetes mellitus in an infant, Lancet 1: 1048–1049.PubMedCrossRefGoogle Scholar
  109. Peig, M., Ercilla, G., Milan, M., Gomis, R., 1981, Post-mumps diabetes mellitus, Lancet 1: 1007.PubMedCrossRefGoogle Scholar
  110. Perlman, L. V., 1961, Familial incidence of diabetes in hyperthyroidism, Ann. Intern. Med. 55: 796–799.PubMedGoogle Scholar
  111. Plotkin, S. A., and Kaye, R., 1970, Diabetes mellitus and congenital rubella, Pediatrics 46: 650–651.PubMedGoogle Scholar
  112. Prince, G. A., Jenson, A. B., Billups, L. C., and Netkins, A. L., 1978, Infection of human pancreatic beta cell cultures with mumps virus, Nature 271: 158–161.PubMedCrossRefGoogle Scholar
  113. Rawls, W. E., Melnick, J. L., Rosenberg, H. S., and Bayatpoor, M., 1965, Spontaneous virus carrier cultures and postmortem isolation of virus from infants with congenital rubella, Proc. Soc. Exp. Biol. Med. 120: 623–626.PubMedGoogle Scholar
  114. Rawls, W. E., and Melnick, J. L., 1966, Rubella virus carrier cultures derived from congenitally infected infants, J. Exp. Med. 123: 795–816.PubMedCrossRefGoogle Scholar
  115. Ray, C. G., Palmer, J. P., Grossley, J. R., and Williams, R. H., 1980, Coxsackievirus antibody responses in juvenile-onset diabetes mellitus, Clin. Endocrinol. 12: 375–378.CrossRefGoogle Scholar
  116. Rayfield, E. J., and Seto, Y., 1981, Viruses, in: Handbook of Diabetes Mellitus, Vol. I, EtiologylHormone Physiology (M. Brownlee, ed.), pp. 95–120. Garland STPM Press, New York.Google Scholar
  117. Reddy, C. M., and Crump, E. P., 1976, Diabetes mellitus following mumps, J. Natl. Med. Assoc. 68: 459–460.PubMedGoogle Scholar
  118. Rekosh, D. M., 1978, The molecular biology of picomoviruses, in: The Molecular Biology of Animal Viruses ( D. P. Nayak, ed.), pp. 63–110, Marcel Dekker, New York.Google Scholar
  119. Richens, E. R., and Jones, W. G., 1981, Islet cell antibodies and mumps, Lancet 1: 507–508.PubMedCrossRefGoogle Scholar
  120. Richens, E. R., Ancil, R. J., and Hartog, M., 1976, Autoimmunity and viral infections in diabetes mellitus, Clin. Exp. Immunol. 23: 40–46.PubMedGoogle Scholar
  121. Rodey, G. E., White, N., Frazer, T., Duquesnoy, R. J., and Santiago, J. V., 1979, HLA-DR specificities among black Americans with juvenile-onset diabetes, N. Engl. J. Med. 301: 810–812.PubMedCrossRefGoogle Scholar
  122. Rubinstein, P. Suciu-foca, N., Nicholson, J. F., 1977, Genetics of juvenile diabetes mellitus: A recessive gene closely linked to HLA D with 50 percent penetrance, N. Engl. J. Med. 297: 1036–1040.Google Scholar
  123. Ruddle, N. H., 1979, Delayed hypersensitivity to soluble antigens in mice. II. Analysis in vitro, Int. Arch.Allergy Appl. Immunol. 58: 44–52.CrossRefGoogle Scholar
  124. Samantray, S. K., Christopher, S., Mukundan, P., and Johnson, S. C., 1977, Lack of relationship between viruses and human diabetes mellitus, N.Z. J. Med., 7: 139–142.CrossRefGoogle Scholar
  125. Santoli, D., and Koprowski, H., 1979, Mechanisms of activation of human natural killer cells against tumor and virus-infected cells, Immunol. Rev. 44: 125–164.PubMedCrossRefGoogle Scholar
  126. Santoli, D., Trinchieri, G., Zmijewski, C., and Koprowski, H., 1976, HLA-related control of spontaneous and antibody-dependent cell-mediated cytotoxic activity in humans. J. Immunol., 117: 765–772.PubMedGoogle Scholar
  127. Schmidt, M. B., 1902, Über die Beziehung der Langerhanssche Inseln des Pankreas zum Diabetes Mellitus,MMW 49: 51–55.Google Scholar
  128. Sinaniotis, C. A., Daskalopolou, E., Lapatsanis, P., Doxiadis, S., 1975, Diabetes mellitus after mumps vaccination, Arch. Dis. Child. 50: 749–750.PubMedCrossRefGoogle Scholar
  129. Smith, M. G, and Vellios, F., 1950, Inclusion disease or generalized salivary gland virus infection, Arch. Pathol. 50: 862–884.Google Scholar
  130. Smithells, R. W., Sheppard, S., Marshall, W. C., and Peckham, C., 1978, Congenital rubella and diabetes mellitus Lancet 1: 439.CrossRefGoogle Scholar
  131. Sultz, H. A. Hart, B. A., Zielezny, M., Schlesinger, E. R., 1975, Is mumps virus an etiologic factor in juvenile diabetes mellitus?, J. Pediatr. 86: 654–656.PubMedCrossRefGoogle Scholar
  132. Tesh, R. B., 1978, The prevalence of encephalomyocarditis virus neutralizing antibodies among various human populations, Am. J. Trop. Med. Hyg. 27: 144–149.PubMedGoogle Scholar
  133. Tsutsumi, H., Chiba, Y., Abo, W., Chiba, S., and Nakao, T., 1980, T cell-mediated cytotoxic response to mumps virus in humans, Infect. Immun. 30: 129–134.PubMedGoogle Scholar
  134. von Meyenburg, H., 1940, Uber “Insulitis” bei Diabetes, Schweiz. Med. Wochenschr. 21: 554.Google Scholar
  135. Walker, S. M., Lee, S. C., and Lucas, Z. J., 1976, Cytotoxic activity of lymphocytes. VI. Heterogeneity of cytotoxins in supernatants of mitogen-activated lymphocytes, J. Immunol., 116: 807–815.PubMedGoogle Scholar
  136. Ward, K. P., Galloway, W. H., and Auchterlonie, I. A., 1979, Congenital cytomegalovirus infection and diabetes, Lancet 1: 497.PubMedCrossRefGoogle Scholar
  137. Warren, S., 1927, The pathology of diabetes in children, JAMA,: 88: 99–101.Google Scholar
  138. Weller, T. H., and Craig, J. M., 1949, The isolation of mumps virus at autopsy, Am. J. Pathol. 25: 1105–1115.PubMedGoogle Scholar
  139. West, R., Belmont, E., Colle, M. P., Crepeau, M. P., Wilkins, J., and Poirier, R., 1979, Epidemiologic survey of juvenile onset diabetes in Montreal, Diabetes 28: 690–693.PubMedCrossRefGoogle Scholar
  140. West, R., Colle, W. E., Belmonte, M. M., Tangle, A., Guttmann, R., Hynie, I., Thomas, D., Wilkins, J., Poirier, R., and Crepeau, M. P., 1981, Prospective study of insulin-dependent diabetes mellitus, Diabetes 30: 584–589.PubMedCrossRefGoogle Scholar
  141. Wilson, C., Connolly, J. H., and Thomson, D., 1977, Coxsackie B-2 virus infection and acute-onset diabetes in a child, Br. Med. J. 1: 1008.PubMedCrossRefGoogle Scholar
  142. Wilson, G. L., D’Andrea, B. J., Bellomo, S. C., and Craighead, J. C., 1980, Encephalomyocarditis virus infection of cultured murine pancreatic beta cells, Nature 285: 112–113.PubMedCrossRefGoogle Scholar
  143. Witte, C. W., and Schanzer, B., 1968, Pancreatitis due to mumps, JAMA 203:1068–1069. Woodruff, J. F., 1980, Viral myocarditis: A review, Am. J. Pathol. 101: 425–484.Google Scholar
  144. Yoon, J. W., Lesniak, M. A., Fussganger, R., and Notkins, A. L., 1976, Genetic differences in susceptibility of pancreatic cells to virus induced diabetes mellitus, Nature 264: 178–180.PubMedCrossRefGoogle Scholar
  145. Yoon, J.-W., Huang, S. W., MacLaren, N. K., Wheeler, C. J., Selvaggio, S. S., and Notkins, A. L., 1977, Antibody to encephalomyocarditis virus in juvenile diabetes, N. Engl. J. Med. 297: 1235–1236.PubMedGoogle Scholar
  146. Yoon, J. W., Onodera, T., Jenson, A. B., and Notkins, A. B., 1978, Virus-induced diabetes mellitus. XI. Replication of Coxsackie B3 virus in human pancreatic beta cell cultures, Diabetes 27: 778–781.PubMedCrossRefGoogle Scholar
  147. Yoon, J. W., Austin, M., Onodera, T., and Notkins, A. L., 1979, Virus induced diabetes mellitus. Isolation of a virus from the pancreas of a child with diabetic ketoacidosis, N. Engl. J. Med. 300: 1173–1179.PubMedCrossRefGoogle Scholar
  148. Yoon, J. W., McClintock, P. R., Onodera, T., and Notkins, A. L., 1980, Virus-induced diabetes mellitus: XVIII. Inhibition by a nondiabetogenic variant of encephalomyocarditis virus, J. Exp. Med. 152: 878–892.PubMedCrossRefGoogle Scholar
  149. Yoon, J. W., Selvaggio, S., Onodera, T., Wheeler, J., and Jenson, A. B., 1981, Infection of cultured human pancreatic cells with reovirus type 3, Diabetologia 20: 462–467.PubMedCrossRefGoogle Scholar
  150. Ziring, P. R., 1977, Congenital rubella: The teenage years, Pediatr. Ann. 6: 762–770.PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1984

Authors and Affiliations

  • S. A. Huber
    • 1
  • B. R. MacPherson
    • 1
  1. 1.Department of PathologyUniversity of VermontBurlingtonUSA

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