Summary
Infections with Coxsackie viruses (especially Coxsackie B4) are thought to be involved in the pathogenesis of diabetes. Many interdependent variables determine the outcome of an infection with a Coxsackie virus, one of them being the tropism of the virus for a specific tissue. The extent to which Beta cell tropic variants of Coxsackie B4 virus occur naturally was assessed. Human isolates of this virus were tested in an in vitro system in which elevated insulin release from infected islets incubated at a non-stimulatory (2 mmol/l) glucose concentration appears to be related to viral attack. Using this technique, 8/24 isolates tested, impaired secretory function in mouse islets. Some strains of Coxsackie B4 virus, therefore, will directly infect mouse islets in vitro leading to changes in islet cell function. In conclusion, these findings confirm that variants of Coxsackie B4 virus with the potential to damage Beta cells occur quite frequently in the natural population. In certain circumstances the damage they inflict on Beta cells may cause destruction of these cells, or precipitate overt diabetes.
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References
Gamble DR, Taylor KW (1969) Seasonal incidence of diabetes mellitus. Br Med J 3: 631–663
Gamble DR, Kinsley ML, Fitzgerald MG, Bolton R, Taylor KW (1969) Viral antibodies in diabetes mellitus. Br Med J 3: 627–630
Yoon JW, Austin M, Onodera T, Notkins AL (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
Champsaur H, Dussaix E, Samolyk D, Fabre M, Bach Ch, Assan R (1980) Diabetes and Coxsackie virus B5 infection. Lancet I: 251
Gladisch R, Hofmann W, Waldherr R (1976) Myokarditis und Insulitis nach Coxsackie-Virus-Infektion. Z Kardiol 65: 837–849
Nigro G, Pacella ME, Patane E, Midulla M (1986) Multisystem Coxsackievirus B6 infection with findings suggestive of diabetes mellitus. Eur J Ped 145: 557–559
Chatterjee NK, Haley TM, Nejman C (1985) Functional alterations in pancreatic β cells as a factor in virus-induced hyperclycemia. J Biol Chem 260: 12786–12791
Coleman TJ, Gamble DR, Taylor KW (1973) Diabetes in mice after Coxsackie B4 virus infection. Br Med J 3: 25–27
Szopa TM, Dronfield DM, Ward T, Taylor KW (1989) In vivo infection of mice with Coxsackie B4 virus induces long-term functional changes in pancreatic islets with minimal alteration in blood glucose. Diab Med 6: 314–319
Szopa TM, Gamble DR, Taylor KW (1986) Coxsackie B4 virus induces short-term changes in the metabolic functions of mouse pancreatic islets in vitro. Cell Biochem Funct 4: 181–187
Hartig PC, Madge GE, Webb SR (1983) Diversity within a human isolate of Coxsackie B4: relationship to viral-induced diabetes. J Med Virol 11: 23–30
Gauntt CJ (1988) The possible role of virus variants in pathogenesis. In: Bendinelli M, Friedman H (eds) Coxsackieviruses. Plenum Press, New York, pp 159–173
Prabhakar BS, Haspel MV, McClintock PR and Notkins AL (1982) High frequency of antigenic variants among naturally occurring human Coxsackie B4 isolates identified by monoclonal antibodies. Nature 300: 374–376
Kuno S, Itagaki A, Yamazaki I, Katsumoto T, Kurimura T (1984) Pathogenicity of newly isolated Coxsackievirus B4 for mouse pancreas. Acta Virol 28: 433–436
Jordan GW, Bolton V, Schmidt N (1985) Diabetogenic potential of Coxsackie B viruses in nature. Arch Virol 86: 213–221
Craighead JE (1966) Pathogenicity of the M and E variants of the encephalomyocarditis (EMC) virus. I. Myocardiotropic and neurotropic properties. Am J Pathol 48: 333–345
Howell SE, Taylor KW (1968) Potassium ions and the secretion of insulin by islets of Langerhans incubated in vitro. Biochem J 108: 17–24
Gey GO, Gey MK (1936) The maintenance of normal hormone cells and tumour cells in continuous culture. Am J Cancer 27: 45–76
Hales CN, Randle PJ (1963) Immunoassay of insulin with insulin antibody precipitate. Biochem J 88: 137–146
Craighead JE, McLane MF (1968) Diabetes mellitus: induction in mice by encephalomyocarditis virus. Science 162: 913–914
Ross ME, Hayashi K, Notkins AL (1974) Virus-induced pancreatic disease: alteration in concentration of glucose and amylase in blood. J Infect Dis 129: 669–676
Johnston C, Raghu P, McCulloch DK, Beard JC, Ward WK, Klaff LJ, McKnight B, Bergman RN, Palmer JP (1987) β-cell function and insulin sensitivity in non-diabetic HLA-identical siblings of insulin-dependent diabetics. Diabetes 36: 829–837
Heaton DA, Millward BA, Gray IP, Yun T, Hales CN, Pyke DA, Leslie RDG (1987) Evidence for β-cell dysfunction which does not lead to diabetes: a study of identical twins of insulin-dependent diabetics. Br Med J 294: 145–146
Toniolo A, Onodera T, Jordan G, Yoon JW, Notkins AL (1981) Virus induced diabetes mellitus. Glucose abnormalities produced in mice by the six members of the Coxsackie B virus group. Diabetes 31: 496–499
Yoon JW, London WT, Curfman BL, Brown RL, Notkins AL (1986) Coxsackie Virus B4 produces transient diabetes in nonhuman primates. Diabetes 35: 712–716
Pasternak CA, Micklem KJ (1987) Virally induced alterations in cellular permeability: a basis of cellular and physiological damage. Bioscience Rep 1: 431–448
Jenkins O, Booth JD, Minor PD, Almond JW (1987) The complete nucleotide sequence of Coxsackievirus B4 and its comparison to other members of the picornaviridae. J Gen Virol 68: 1835–1848
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Szopa, T.M., Ward, T., Dronfield, D.M. et al. Coxsackie B4 viruses with the potential to damage Beta cells of the islets are present in clinical isolates. Diabetologia 33, 325–328 (1990). https://doi.org/10.1007/BF00404634
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DOI: https://doi.org/10.1007/BF00404634