Abstract
Chronic progressive demyelination in canine distemper virus (CDV) infection is associated with persistence of the virus in the nervous system. We studied persistence by examining expression of CDV mRNA corresponding to all genes of the virus as well as genomic CDV RNA in brain sections of dogs with acute and chronic demyelinating disease. All virus mRNAs were expressed in acute demyelinating lesions in a way similar to that seen in lymphoid tissues, the primary replication site of CDV. Their distribution corresponded very well with immunohistochemical detection of virus protein. In contrast, much more CDV mRNA than virus protein was found in gray matter areas suggesting that translation of CDV can be impaired in nervous distemper. Virus protein and RNA were cleared from chronic inflammatory demyelinating lesions. mRNA corresponding to the distal genes (F; H; L) of CDV disappeared first in inflammatory lesions for technical reasons associated with the particular mode of transcription of morbilliviruses. CDV RNA and protein persisted in chronically ill dogs in other areas of the CNS in which inflammation had not occurred. Our results suggest that persistence of CDV is favored by non-cytolytic spread of the virus and restricted infection of certain cells with reduced viral protein expression. Both tend to delay immune recognition of the virus.
Similar content being viewed by others
References
Alldinger S, Baumgärtner W, Orvell C (1993) Restricted expression of viral surface proteins in canine distemper encephalitis. Acta Neuropathol 85:635–645
Appel MJG, Gillespie JH (1972) Canine distemper virus. Virol Monogr 11:1–96
Appel MJG, Shek WR, Summers BA (1982) Lymphocyte-mediated immune cytotoxicity in dogs infected with virulent canine distemper virus. Immunology 37:592–600
Bollo E, Zurbriggen A, Vandevelde M, Fankhauser R (1986) Canine distemper virus clearance in chronic inflammatory demyelination. Acta Neuropathol (Berl) 72:69–73
Botteron C, Zurbriggen A, Griot C, Vandevelde M (1992) Canine distemper virus-immune complexes induce bystander degeneration of oligodendrocytes. Acta Neuropathol 83:402–407
Cattoretti G, Pileri S, Parravicini C, Becker MHG, Poggi S, Bifulco C, Key G, D'Amato L, Sabattini E, Feudale E, Reynolds F, Gerdes J, Rilke F (1993) Antigen unmasking on formalinfixed, paraffin-embedded tissue sections. J Pathol 171:83–98
Friedlander JM, Summers BA, Appel MJG (1985) Persistence of virulent canine distemper virus in lymphoblastoid cell lines. Arch Virol 86:47–62
Fujinami RS, Oldstone MB (1983) Antigenic modulation: a mechanism of viral persistence. Prog Brain Res 59:105–111
Griot G, Bürge T, Vandevelde M, Peterhans E (1989) Antibody-induced generation of reactive oxygen radicals by brain macrophages in canine distemper encephalitis: a mechanism for bystander demyelination. Acta Neuropathol 78:396–403
Higgins RJ, Child G, Vandevelde M (1989) Chronic relapsing demyelinating encephalomyelitis associated with persistent spontaneous canine distemper virus infection. Acta Neuropathol 77:441–444
Imagawa DT, Howard EB, Vant Pelt LF, Ryan CF, Bui HD, Shapshak P (1980) Isolation of canine distemper virus from dogs with chronic neurological diseases. Proc Soc Exp Biol Med 164:355–362
Kimoto T (1986) In vitro and in vivo properties of the virus causing natural canine distemper encephalitis. J Gen Virol 67: 487–503
Kingsbury DW (1990) Parymyxoviridae and their replication. In: Fields BN, Knipe DM, Chanock RM, Hirsch MS, Melrick JL, Monath TP, Roizman B (es) Virology. Raven Press, New York, pp 945–962
Metzler AE, Higgins RJ, Krakowka S, Koestner A (1980) Persistent in vitro interaction of virulent and attenuated canine distemper virus with bovine cells. Arch Virol 66:329–339
Metzler AE, Krakowka S, Azthelm MK (1984) In vitro propagation of canine distemper virus: establishment of persistent infection in Vero cells. Am J Vet Res 45:2211–2215
Mitchell WJ, Russell SE, Clark DK, Rima BK, Appel MJ (1987) Identification of negative strand and positive strand RNA of canine distemper virus in animal tissues using singlestranded RNA probes. J Virol Methods 18:121–131
Pearce Kelling S, Mitchell WJ, Summers BA, Appel MJ (1990) Growth of canine distemper virus in cultured astrocytes: relationship to in vivo persistence and disease. Microb Pathog 8: 71–82
Schneider Schaulies S, Liebert UG, Baczko K, ter Meulen V (1990) Restrioted expression of measles virus in primary rat astroglial cells. Virology 177:802–806
ter Meulen V, Martin SJ (1976) Genesis and maintenance of a persistent infection by canine distemper virus. J Gen Virol 32: 431–440
Tobler LH, Imagawa DT (1984) Mechanism of persistence with canine distemper virus: difference between a laboratory strain and an isolate from a dog with chronic neurologic disease. Intervirology 21:77–86
Vandevelde M, Kristensen B, Braund KG, Greene CE, Swango LJ, Hoerlein BF (1980) Chronic canine distemper virus encephalitis in mature dogs. Vet Pathol 17:17–28
Vandevelde M, Higgins RJ, Kristensen B, Kristensen F, Steck AJ, Kihm U (1982) Demyelination in experimental canine distemper virus infection: immunological, pathologic, and immunohistological studies. Acta Neuropathol (Berl) 56: 285–293
Vandevelde M, Kristensen F, Kristensen B, Steck AJ, Kihm U (1982) Immunological and pathological findings in demyelinating encephalitis associated with canine distemper virus infection. Acta Neuropathol (Berl) 56:1–8
Reference deleted
Vandevelde M, Zurbriggen A, Higgins RJ, Palmer D (1985) Spread and distribution of viral antigen in nervous canine distemper. Acta Neuropathol (Berl) 67:211–218
Wisniewski H, Raine CS, Kay WJ (1972) Observations on viral demyelinating encephalomyelitis: canine distemper. Lab Invest 26:589–599
Yamawaki M, Zurbriggen A, Richard A, Vandevelde M (1993) Saponin treatment for in situ hybridization maintaining good morphological preservation. J Histochem Cytochem 41: 105–109
Zurbriggen A, Müller C, Vandevelde M (1993) In situ hybridization of virulent canine distemper virus in brain tissue, using digoxigenin-labelled probes. Am J Vet Res 54: 1457–1461
Zurbriggen A, Yamawaki M, Vandevelde M (1993) Restricted canine distemper virus infection of oligodendrocytes. Lab Invest 68:277–284
Zubriggen A, Graber HU, Wagner A, Vandevelde M (1995) Canine distemper virus persistence in the nervous system is associated with non-cytolytic selective virus spread. J Virol (in press)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Müller, C.F., Fatzer, R.S., Beck, K. et al. Studies on canine distemper virus persistence in the central nervous system. Acta Neuropathol 89, 438–445 (1995). https://doi.org/10.1007/BF00307649
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00307649