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. 1982;58(1):1–8. doi: 10.1007/BF00692691

Primary demyelination in experimental canine distemper virus induced encephalomyelitis in gnotobiotic dogs

Sequential immunologic and morphologic findings

R J Higgins 1,✉, S G Krakowka 3, A E Metzler 4, A Koestner 5
PMCID: PMC7086558  PMID: 7136512

Summary

Experimental infection of gnotobiotic Beagle dogs at 21 days of age with neurovirulent R252 strain of canine distemper virus (R252-CDV) resulted in a non-suppurative encephalomyelitis. Segmental internodal primary demyelination was found in almost 90% of the dogs from 27 days post inoculation (DPI). Ultrastructurally demyelination was initiated by the insertion of CDV-infected astrocytic processes at nodes of Ranvier with subsequent cleavage of well-preserved myelin from the axolemma. CDV-infected macrophages were consistently involved in myelin phagocytosis. Some remyelination of denuded axons occurred after 35 DPI. Persistent productive infection of the choroid plexus and ependyma in the fourth ventricle was consistently associated with subependymal foci of demyelination.

Primary demyelination occurred without detectable CDV-specific virus-neutralizing (CDV-VN) antibody in either serum or cerebrospinal fluid (CSF). There were no immunoglobulin deposits or inflammatory cells within the lesions. These findings indicate that both direct CDV antibody-dependent and CDV antibody-dependent cell-mediated immune mechanisms of cytolysis or myelin destruction are not involved in the genesis of initial primary demyelination. The sequential morphologic and serologic findings in this model of demyelinating encephalomyelitis indicate that direct virus-induced injury has a major role in both the initiation and early progression of primary demyelination.

Key words: Canine, Canine distemper virus, Demyelination, Encephalomyelitis, Antibodies

Footnotes

Supported by The State of Ohio Canine Research Fund and Grant Number 2 ROI NS 14821, National Institutes of Health, USA. A.E.M. was supported by the Schweizerische Stiftung für Medizinisch-biologische Stipendien, Basel and the Janggen-Pohen-Stiftung, St. Gallen, Switzerland

References

  • 1.Appel MJG, Gillespie JH. Canine distemper virus. Virol Monogr. 1972;10:1–96. [Google Scholar]
  • 2.Appel MJG, Robson DS. A micro-neutralization test for canine distemper virus. Am J Vet Res. 1973;34:1459–1463. [PubMed] [Google Scholar]
  • 3.Cammer W, Bloom BR, Norton WT, Gordon S. Degradation of basic protein in myelin by neutral proteases secreted by stimulated macrophages: A possible mechanism of inflammatory demyelination. Proc Natl Acad Sci USA. 1978;75:1554–1558. doi: 10.1073/pnas.75.3.1554. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Greisemer RG. The gnotobiotic dog. Lab Anim Care. 1963;13:643–649. [PubMed] [Google Scholar]
  • 5.Higgins RJ, Krakowka S, Metzler AE, Koestner A. Experimental canine distemper encephalomyelitis in neonatal gnotobiotic dogs — a sequential ultrastructural study. Acta Neuropathol (Berl) 1982;57:287–295. doi: 10.1007/BF00692185. [DOI] [PubMed] [Google Scholar]
  • 6.Ho CK, Babiuk LA. Immune mechanisms against canine distemper. Immunology. 1980;39:231–237. [PMC free article] [PubMed] [Google Scholar]
  • 7.Innes JRM, Saunders LZ. Comparative neuropathology. New York: Academic Press; 1962. pp. 373–384. [Google Scholar]
  • 8.Kennedy PGE, Lisak RP, Raff MC. Cell type-specific markers for human glial and neuronal cells in culture. Lab Invest. 1980;43:342–351. [PubMed] [Google Scholar]
  • 9.Koestner A. Animal model — distemper-associated demyelinating encephalomyelitis. Am J Pathol. 1975;78:361–364. [PMC free article] [PubMed] [Google Scholar]
  • 10.Koestner A, McCullough B, Krakowka S, Long JF, Olsen RG. Canine distemper: A virus-induced demyelinating encephalomyelitis. In: Zeman W, Lenette, editors. Slow virus diseases. Baltimore: Williams & Wilkins; 1974. pp. 86–101. [Google Scholar]
  • 11.Krakowka S, Cockerell G, Koestner A. Effects of canine distemper virus infection on lymphoid function in vitro and in vivo. Infect Immun. 1975;11:1069–1078. doi: 10.1128/iai.11.5.1069-1078.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Krakowka S, Higgins RJ, Metzler AE. Plasma phase viremia in canine distemper virus in gnotobiotic dogs. J Infect Dis. 1980;134:629–632. [Google Scholar]
  • 13.Krakowka S, Koestner A. Age-related susceptibility to infection with canine distemper virus in gnotobiotic dogs. J Infect Dis. 1976;134:629–632. doi: 10.1093/infdis/134.6.629. [DOI] [PubMed] [Google Scholar]
  • 14.Krakowka S, Long D, Mezza R, Mador R, Koestner A. Derivation and maintenance of gnotobiotic dogs. Lab Anim Sci. 1978;28:327–330. [PubMed] [Google Scholar]
  • 15.Krakowka S, Mador RA, Koestner A. Canine distemper virus-associated encephalitis: Modification by passive antibody administration. Acta Neuropathol (Berl) 1978;43:235–241. doi: 10.1007/BF00691584. [DOI] [PubMed] [Google Scholar]
  • 16.Krakowka S, Higgins RJ, Koestner A. Canine distemper virus: Review of structural and functional modulations in lymphoid tissues. Am J Vet Res. 1980;41:284–292. [PubMed] [Google Scholar]
  • 17.Lampert PW. Demyelination and remyelination in experimental allergic encephalomyelitis: further electron microscopic observations. J Neuropathol Exp Neurol. 1965;24:371–380. doi: 10.1097/00005072-196501000-00002. [DOI] [PubMed] [Google Scholar]
  • 18.Lampert PW. Autoimmune and virus-induced demyelinating diseases. Am J Pathol. 1978;91:176–197. [PMC free article] [PubMed] [Google Scholar]
  • 19.Mador R, Krakowka S, Koestner A. A procedure for processing central nervous system tissue for immunofluorescence, light and electron microscopic evaluation. Am J Vet Res. 1974;38:1946–1949. [PubMed] [Google Scholar]
  • 20.McCullough B, Krakowka A, Koestner A. Experimental canine distemper virus-induced demyelination. Lab Invest. 1974;31:216–222. [PubMed] [Google Scholar]
  • 21.McCullough B, Krakowka S, Koestner A, Shadduck J. Demyelinating activity of distemper virus isolates in gnotobiotic dogs. J Infect Dis. 1974;130:343–350. doi: 10.1093/infdis/130.4.343. [DOI] [PubMed] [Google Scholar]
  • 22.Prineas JW, Connell F. Remyelination in multiple sclerosis. Ann Neurol. 1979;5:22–31. doi: 10.1002/ana.410050105. [DOI] [PubMed] [Google Scholar]
  • 23.Raine CS. On the development of CNS lesions in natural canine distemper encephalomyelitis. J Neurol Sci. 1976;30:13–28. doi: 10.1016/0022-510x(76)90251-3. [DOI] [PubMed] [Google Scholar]
  • 24.Shek WR, Schultz RD, Appel MJG. Natural and immune cytolysis of canine distemper virus-infected target cells. Infect Immun. 1980;28:724–734. doi: 10.1128/iai.28.3.724-734.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Snyder DH, Valsamis MP, Stone SH, Raines CS. Progressive demyelination and reparative phenomena in chronic experimental allergic encephalomyelitis. J Neuropathol Exp Neurol. 1975;34:209–215. doi: 10.1097/00005072-197505000-00001. [DOI] [PubMed] [Google Scholar]
  • 26.Summers BA, Greisen HA, Appel MJG. Early events in canine distemper demyelinating encephalomyelitis. Acta Neuropathol (Berl) 1979;46:1–10. doi: 10.1007/BF00684797. [DOI] [PubMed] [Google Scholar]
  • 27.Vandevelde M, Kristensen B. Observations on the distribution of canine distemper virus in the central nervous system of dogs with demyelinating encephalomyelitis. Acta Neuropathol (Berl) 1977;40:233–236. doi: 10.1007/BF00691959. [DOI] [PubMed] [Google Scholar]
  • 28.Lisiak JA, Vandevelde M. Polioencephalomalacia associated with canine distemper virus infection. Vet Pathol. 1979;16:650–660. doi: 10.1177/030098587901600603. [DOI] [PubMed] [Google Scholar]
  • 29.Weiner LP. Pathogenesis of demyelination induced by a mouse hepatitis virus (JHM virus) Arch Neurol. 1973;28:298–303. doi: 10.1001/archneur.1973.00490230034003. [DOI] [PubMed] [Google Scholar]
  • 30.Weiner LP, Stohlman SA. Viral models of demyelination. Neurology. 1978;28:111–114. doi: 10.1212/wnl.28.9_part_2.111. [DOI] [PubMed] [Google Scholar]
  • 31.Wisniewski HM. Immunopathology of demyelination in autoimmune diseases and virus infections. Br Med Bull. 1977;33:54–59. doi: 10.1093/oxfordjournals.bmb.a071397. [DOI] [PubMed] [Google Scholar]
  • 32.Wisniewski HM, Raine CS, Kay WJ. Observations on viral demyelinating encephalomyelitis: Canine distemper. Lab Invest. 1972;26:589–599. [PubMed] [Google Scholar]

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