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Demyelination in experimental canine distemper virus infection: Immunological, pathologic, and immunohistological studies

Summary

White matter lesions were induced in the brains of eight of nine dogs by means of experimental canine distemper virus (CDV) infection. Dogs were killed at 21, 24, 31, and 42 days after infection. Lymphocyte responsiveness to Con A and PHA stimulation in vitro was severely suppressed up to 31 days post infection (p.i.), followed by partial recovery as tested at 42 days p.i. Anti-CDV neutralizing antibody response was very weak in most dogs. There was a weak increase in antimyelin and antimyelin basic protein antibodies in most dogs during the course of the experiment. Dogs killed up to 31 days p.i. developed non-inflammatory demyclinating lesions in which no immunoglobulin could be detected. One of the three dogs that were killed at 42 days p.i. developed severe inflammatory demyelination. This was the only dog with a strong anti-MBP antibody response in the CSF and immunoglobulin demonstrated in demyelinating lesions. The present study supports previous observations that demyelination in acute CDV infection is not an immune mediated lesion but that these lesions may progress as a result of the local immune response. It is uncertain at this stage whether the local immune reaction specifically causes myelin destruction or whether bystander demyelination occurs in chronic CDE.

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References

  1. Allen IV (1981) Annotation. The pathology of multiple sclerosis: Fact, fiction and hypothesis. Neuropathol Appl Neurobiol 7:169–182

  2. Appel MJG (1969) Pathogenesis of canine distemper. Am J Vet Res 30:1167–1182

  3. Appel MJG, Gillespie JH (1972) Canine distemper virus. Virology monographs. Springer, Wien New York

  4. Appel MJG, Robson DS (1973) A microneutralization test for canine distemper virus. Am J Vet Res 34:1459–1463

  5. Bornstein MB, Raine CS (1976) The initial structural lesion in serum-induced demyelination in vitro. Lab Invest 35:391–401

  6. Brosnan CF, Stoner GL, Bloom BR, Wisniewski HM (1977) Studies on demyelination by activated lymphocytes in the rabbit eye. II. Antibody-dependent cell-mediated demyelination. J Immunol 118:2103–2110

  7. Edgington TS, Dalessio DJ (1970) The assessment by immunofluorescence methods of humoral anti-myelin antibodies in man. J Immunol 105:248–255

  8. Fankhauser R (1951) Encephalitis und Hard-pad-Symptom beim Hunde. Schweiz Arch Tierheilkd 93:796–821

  9. Fankhauser R (1962) The cerebrospinal fluid. In: Innes JRM, Saunders LZ (eds) Comparative neuropathology. Academic Press, New York London

  10. Frauchiger E, Fankhauser R (1957) Vergleichende Neuropathologie des Menschen und der Tiere. Springer, Berlin Göttingen Heidelberg

  11. Golds EE, Braun P (1978) Cross-linking studies on the conformation and dimerisation of myelin basic protein in solution. J Biol Chem 253:8171–8177

  12. Hoorlein BF (1978) Canine neurology, 3rd edn. Saunders, Philadelphia London Toronto

  13. Koestner A, McCullough B, Krakowka GS, Long JF, Olsen RF (1974) Canine distemper, a virus-induced demyelinating encephalomyelitis. In: Zeman W, Lenette EH (eds) Slow virus diseases. Williams and Wilkins, Baltimore, pp 86–101

  14. Koestner A (1975) Animal model of human disease. Subacute sclerosing panencephalitis, multiple sclerosis. Am J Pathol 78:361–364

  15. Krakowka S, McCullough B, Koestner A, Olsen R (1973) Myelinspecific autoantibodies associated with central nervous system demyelination in canine distemper virus infection. Infect Immun 8:819–827

  16. Krakowka S, Koestner A (1976) Age-related susceptibility to infection with canine distemper virus in gnotobiotic dogs. J Infect Dis 134:629–632

  17. Krakowka S, Higgins RJ, Koestner A (1980) Canine distemper virus: Review of structural and functional modulations in lymphoid tissues. Am J Vet Res 41:284–292

  18. Krakowka S, Wallace AL, Koestner A (1981) Shared antigenic determinants between brain and thymus-derived lymphocytes in dogs. Implications regarding the significance of antimyelin antibodies in demyelination. Acta Neuropathol (Berl) 54:75–82

  19. Kristensen B, Kristensen F, Vandevelde M, Higgins RJ, de Weck AL (1982) Canine lymphocyte cultures in vitro: Evaluation of peripheral blood lymphocyte response to mitogens. J Vet Immunol Immunopathol (in press)

  20. Kristensen F, Kristensen B, Vandevelde M, Higgins RJ, de Weck AL (1982) Analysis of the in vitro activation and proliferation process in lymphocytes deriving from canine thymus and mesenteric lymphnode. J Vet Immunol Immunopathol (in press)

  21. Lassmann H, Kitz K, Wisniewski HM (1981) The development of periventricular lesions in chronic relapsing experimental allergic encephalomyelitis in guinea pigs: A light-and scanning electronmicroscopic study. Neuropathol Appl Neurobiol 7:1–11

  22. Martin JR, Nathanson N (1979) Animal models of virus-induced demyelination. In: Zimmerman HM (ed) Progress in neuropathology, vol 4. Raven Press, New York, pp 27–50

  23. McCullough B, Krakowka S, Koestner A (1974) Experimental canine distemper virus-induced lymphoid depletion. Am J Pathol 74:155–165

  24. Moulton JE (1956) Fluorescent antibody studies of demyelination in canine distemper. Proc Soc Exp Biol 91:460–464

  25. Raine CS (1976) On the development of CNS lesions in natural canine distemper encephalomyelitis. J Neurol Sci 30:13–28

  26. Seil FJ (1977) Tissue culture studies of demyelinating disease: A critical review. Ann Neurol 2:345–355

  27. Steck AJ, Tschannen R, Schaefer R (1981) Induction of antimyelin and antioligodendrocyte antibodies by vaccinia virus: Experimental study in the mouse. J Neuroimmunol 1:117–124

  28. Sternberger LA (1979) Immunochemistry, 2nd edn. Wiley & Sons, New York Chichester Brisbane Toronto, pp 122–129

  29. Summers BA, Greisen HA, Appel MJG (1979) Early events in canine distemper demyelinating encephalomyelitis. Acta Neuropathol (Berl) 46:1–10

  30. Vandevelde M, Kristensen B (1977) Observations on the distribution of canine distemper virus in the central nervous system of dogs with demyelinating encephalitis. Acta Neuropathol (Berl) 40:233–236

  31. Vandevelde M, Kristensen B, Braund KG, Greene CE, Swango LJ, Hoerlein BF (1980) Chronic canine distemper virus encephalitis in mature dogs. Vet Pathol 17:17–29

  32. Vandevelde M, Fankhauser R, Kristensen F, Kristensen B (1981) Immunoglobulins in demyelinating lesions in canine distemper encephalitis. Acta Neuropathol (Berl) 54:31–41

  33. Vandevelde M, Kristensen B, Kristensen F, Steck AJ, Kihm U (1982) Immunological and pathological findings in demyelinating encephalitis assocciated with canine distemper virus infection. Acta Neuropathol (Berl) (in press)

  34. Wisniewski HM, Raine CS, Kay WJ (1972) Observations on viral demyelinating encephalomyelitis. Canine distemper. Lab Invest 26:589–599

  35. Wisniewski HM, Brosnan CF, Bloom BR (1980) Bystander and antibody-dependent cell-mediated demyelination. In: Davison AN, Cuzner ML (eds) The suppression of experimental allergic encephalomyelitis and multiple sclerosis. Academic Press, London New York Toronto Sydney San Francisco, pp 45–57

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Supported by Schweizer Nationalfonds grant no. 3.809.81 (to M.V.) and grant no. 3.957.0.80 (to A.J.S.)

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Vandevelde, M., Higgins, R.J., Kristensen, B. et al. Demyelination in experimental canine distemper virus infection: Immunological, pathologic, and immunohistological studies. Acta Neuropathol 56, 285–293 (1982). https://doi.org/10.1007/BF00691260

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Key words

  • Canine distemper encephalitis (CDE)
  • Immunopathology
  • Demyelination
  • Immunoglobulin
  • Local immune response