Skip to main content
PMC home page
Wiley - PMC COVID-19 Collection logoLink to Wiley - PMC COVID-19 Collection
. 2004 Oct 12;4(4):408–416. doi: 10.1002/glia.440040409

Virulent and attenuated canine distemper virus infects multiple dog brain cell types in vitro

Susan Pearce‐Kelling 1,✉, William J Mitchell 2, Brian A Summers 1, Max J G Appel 2
PMCID: PMC7165944  PMID: 1834561

Abstract

Canine Distemper Virus (CDV) produces an encephalitis in dogs that varies with viral strain. We have studied the cell tropisms of two virulent strains (CDV‐SH and CDV A75–17) and an attenuated strain, Rockborn (CDV‐RO), in cultured canine brain cells. Infected cell types were identified by double immunofluorescent labeling of specific cell markers and viral antigens. All viral strains studied produced infection in astrocytes, fibroblasts, and macrophages. Neurons were not infected by CDV A75–17 but were rapidly infected by CDV‐SH and CDV‐RO. Multipolar oligodendrocytes were very rarely infected by any of the virus strains. In contrast, a morphologically distinct subset of bipolar oligodendrocytes were commonly infected by CDV‐SH and CDV‐RO. The kinetics of infection in the astrocytes, oligodendrocytes, neurons, and macrophages varied between strains. Both CDV‐SH and CDV‐RO rapidly infected bipolar oligodendrocytes, astrocytes, neurons, and macrophages by 14 days post infection while infection by CDV A75–17 was delayed until after 28–35 days post infection. The differences in the growth kinetics and cell tropisms for some brain cells, exhibited by the three viral strains examined in this in vitro study, may relate to the different CNS symptoms that these strains produce in vivo.

Keywords: Oligodendrocytes, Neurons, Astrocytes, Canine brain cell cultures, Demyelination, Persistent infection

References

  1. Appel, M. J. G. and Jones, O. R. (1967) Use of alveolar macrophages for cultivation of canine distemper virus. Proc. Soc. Exp. Biol. Med., 126: 571–574. [DOI] [PubMed] [Google Scholar]
  2. Appel, M. J. G. (1969) Pathogenesis of canine distemper. Am. J. Vet. Res., 30: 1167–1181. [PubMed] [Google Scholar]
  3. Appel, M. J. G. (1978) Reversion to virulence of an attenuated canine distemper virus in vivo and in vitro. J. Gen. Virol., 41: 385–393. [Google Scholar]
  4. Baumgartner, W. , Orvell, C. , and Reinacher, M. (1989) Naturally occurring canine distemper virus encephalitis: Distribution and expression of viral polypeptides in nervous tissues. Acta Neuropathol., 78: 504–512. [DOI] [PubMed] [Google Scholar]
  5. Beushausen, S. and Dales, S. (1985) In vivo and in vitro models of demyelinating disease. XI. Tropism and differentiation regulate the infectious process of coronaviruses in primary explants of the rat CNS. Virology, 141: 89–101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Blakemore, W. F. , Summers, B. A. , and Appel, M. G. J. (1989) Evidence of oligodendroglial infection and degeneration in canine distemper encephalomyelitis. Acta Neuropathol., 77: 550–553. [DOI] [PubMed] [Google Scholar]
  7. Elder, G. A. , Potts, B. J. , and Sawyer, M. (1988) Characterization of glial subpopulation in cultures of the ovine central nervous system. Glia, 1: 317–327. [DOI] [PubMed] [Google Scholar]
  8. Eng, L. , Vanderhaegen, J. , Bignami, B. , and Gerstl, B. (1981) An acidic protein isolated from fibrous astrocytes. Brain Res., 28: 351. [DOI] [PubMed] [Google Scholar]
  9. Friedlander, J. M. , Summers, B. A. , and Appel, M. J. G. (1985) Persistence of virulent canine distemper virus in lymphoblastoid cell lines. Arch. Virol., 86: 47–62. [DOI] [PubMed] [Google Scholar]
  10. Glaus, T. , Griot, C. , Richard, A. , Althaus, N. , Herschkowitz, N. , and Vandevelde, M. (1990) Ultrastructural and biochemical findings in brain cell cultures infected with canine distemper virus. Acta Neuropathol., 80: 59–67. [DOI] [PubMed] [Google Scholar]
  11. Johnson, G. , Davidson, R. S. , McNamee, K. C. , Russell, D. G. , and Holborow, E. J. (1982) Fading of immunofluorescence during microscopy a study of the phenomenon and its remedy. J. Immunol. Methods, 55: 231–242. [DOI] [PubMed] [Google Scholar]
  12. Kachar, B. , Behar, T. , and Dubois‐Dalcq, M. (1986) Cell shape and motility of oligodendrocytes cultured without neurons. Cell Tissue Res., 244: 27–38. [DOI] [PubMed] [Google Scholar]
  13. Knapp, P. E. , Bartlett, W. P. , and Skoff, R. P. (1987) Cultured oligodendrocytes mimic in vivo phenotypic characteristics: Cell shape, expression of myelin‐specific antigens, and membrane production. Dev. Biol., 120: 356–365. [DOI] [PubMed] [Google Scholar]
  14. McCarthy, K. D. and de Vellis, J. (1980) Preparation of separate astroglial and oligodendroglial cell cultures from rat cerebral tissue. J. Cell Biol., 85: 890–902. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Pearce‐Kelling, S. , Mitchell, J. M. , Summers, B. A. , and Appel. M. J. G. (1990) Growth of canine distemper virus in cultured astrocytes: Relationship to in vivo persistence and disease. Microb. Pathogen., 8: 71–82. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Raff, M. , Mirsky, R. , Fields, K. , Lisak, R. , Dorfman, S. , Silberberg, D. , Gregson, N. , Leibowitz, S. , and Kennedy, M. (1978) Galactocerebroside is a specific cell‐surface antigenic marker for oligodendrocytes in culture. Nature, 274: 813–816. [PubMed] [Google Scholar]
  17. Raff, M. C. , Miller, R. H. , and Noble, M. (1983) A glial progenitor cell that develops in vitro into an astrocyte or an oligodendrocyte depending upon culture medium. Nature, 303: 390–396. [DOI] [PubMed] [Google Scholar]
  18. Raff, M. C. (1989) Glial cell diversification in the rat optic nerve. Science, 243: 1450–1455. [DOI] [PubMed] [Google Scholar]
  19. Raine, C. S. (1976) On the development of CNS lesions in natural canine distemper encephalomyelitis. J. Neurol. Sci., 30: 13–28. [DOI] [PubMed] [Google Scholar]
  20. Schachner, M. , Schoonmaker, G. , and Hynes, R. (1978) Cellular and subcellular localization of LETS protein in the nervous system. Brain Res., 158: 149. [DOI] [PubMed] [Google Scholar]
  21. Schachner, M. , Kim, S. K. , and Zehnle, R. (1981) Developmental expression in the central and peripheral nervous system of oligodendrocyte cell surface antigens (O antigens) recognized by monoclonal antibodies. Dev. Biol., 83: 328–338. [DOI] [PubMed] [Google Scholar]
  22. Sternberger, L. A. (1979) Immunocytochemistry. J. Wiley and Sons, Inc., New York, pp. 104–169. [Google Scholar]
  23. Stoddart, C. and Scott, F. (1988) Isolation and identification of feline peritoneal macrophages for in vitro studies of coronavirus‐macrophage interactions. J. Leukocyte Biol., 44: 319–328. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Summers, B. A. , Greisen, H. A. , and Appel, M. J. G. (1979) Early events in canine distemper demyelinating encephalomyelitis. Acta Neuropathol., 46: 1–10. [DOI] [PubMed] [Google Scholar]
  25. Summers, B. A. , Greisen, H. A. , and Appel, M. J. G. (1984) Canine distemper encephalomyelitis: Variation with virus strain. J. Comp. Pathol., 94: 65–75. [DOI] [PubMed] [Google Scholar]
  26. The, T. and Feltkamp, T. (1970) Conjugation of fluorescein isothiocyanate to antibodies. II. A reproducible method. Immunology, 18: 875–882. [PMC free article] [PubMed] [Google Scholar]
  27. Vandevelde, M. , Zurbriggen, A. , Dumas, M. , and Palmer, D. (1985) Canine distemper virus does not infect oligodendrocytes in vitro. J. Neurol. Sci., 69: 133–137. [DOI] [PubMed] [Google Scholar]
  28. Wood, J. and Anderson, B. (1981) Monoclonal antibodies to mammalian neurofilaments. Biosci. Rep., 1: 263–268. [DOI] [PubMed] [Google Scholar]
  29. Zurbriggen, A. , Vandevelde, M. , Beranek, C. F. , and Steck, A. (1984) A morphological and immunocytochemical characterization of mixed glial cell cultures derived from neonatal canine brain. Res. Vet. Sci., 36: 270–275. [PubMed] [Google Scholar]
  30. Zurbriggen, A. , Vandevelde, M. , and Dumas, M. (1986) Secondary degeneration of oligodendrocytes in canine distemper virus infection in vitro. Lab. Invest., 54: 424–431. [PubMed] [Google Scholar]
  31. Zurbriggen, A. , Dumas, M. , and Vandevelde, M. (1987a) Neurons in dissociated cannine cell cultures. J. Vet. Med., 34: 673–678. [DOI] [PubMed] [Google Scholar]
  32. Zurbriggen, A. , Vandevelde, M. , and Bollo, E. (1987b) Demyelinating, non‐demyelinating and attenuated canine distemper virus strains induce oligodendroglial cytolysis in vitro. J. Neurol. Sci., 79: 33–41. [DOI] [PubMed] [Google Scholar]
  33. Zurbriggen, A. , Vandevelde, M. , Dumas, M. , Griot, C. , and Bollo, E. (1987c) Oligodendrocyte pathology in canine distemper virus infection in vitro. Acta Neuropathol., 74: 366–373. [DOI] [PubMed] [Google Scholar]

Articles from Glia are provided here courtesy of Wiley

RESOURCES