Summary
Sixteen dogs with naturally occurring acute and chronic canine distemper virus (CDV) encephalitis were examined immunohistochemically for the presence of the five major CDV-specific proteins in the central nervous system. Monoclonal antibodies (mAbs) directed against two, three, four and five epitopes of the nucleo-(N), phospho- (P), fusion (F), and hemagglutinin (H) protein, respectively, and a polyclonal monospecific antibody recognizing the matrix (M) protein were used. Both core proteins and their epitopes, three F protein epitopes and the M protein were demonstrated in all animals examined. A fourth F protein epitope was found only in 13 animals. The H-2 and H-3 epitope of the H protein were detected in 15, the H-1 and H-5 epitope in 14, and the H-4 epitope in 3 animals. All viral proteins were observed in the same types of brain cells including neurons and astrocytes. The N and P protein were demonstrated in nucleus, cytoplasm and cell processes, whereas M, H and F protein were observed in the cytoplasm only and rarely in cell processes. In addition, the M protein was detected occasionally in the nucleus of neurons and reactive astrocytes. Intralesional distribution of CDV-specific proteins varied between core and surface proteins. In acute and subacute lesions without associated inflammation, expression of the M, H and F protein was only slightly diminished compared to the N and P protein. However, plaques with severe inflammation were either devoid of viral antigen or exhibited N-and P protein-specific immunoreactivity exclusively at the periphery, whereas expression of surface proteins was severely reduced or absent. These results are suggestive of restricted synthesis of CDV envelope proteins in acute, and more prominent in chronic, distemper encephalitis.
Similar content being viewed by others
References
Baumgärtner W, Örvell C, Reinacher M (1989) Naturally occurring canine distemper virus encephalitis: distribution and expression of viral polypeptides in nervous tissues. Acta Neuropathol 78:504–512
Blixenkrone-Møller M, Sharma B, Varsanyi T, Hu A, Norrby E, Kövamees J (1992) Sequence analysis of the genes encoding the nucleocapsid protein and phosphoprotein (P) of phocid distemper virus, and editing of the P gene transcript. J Gen Virol 73:885–893
Blixenkrone-Møller M, Svansson V, Appel M, Krogsrud J, Have P, Örvell C (1992) Antigenic relationships between field isolates of morbilliviruses from different carnivores. Arch Virol 123:279–294
Bohn W, Ciampor F, Rutter R, Mannweiler K (1990) Localization of nucleocapsid associated polypeptides in measles virus-infected cells by immunogold labelling after resin embedding. Arch Virol 114:53–64
Bollo E, Zurbriggen A, Vandevelde M, Fankhauser R (1986) Canine distemper virus clearance in chronic inflammatory demyelination. Acta Neuropathol (Berl) 72:69–73
Brown HR, Goller N, Thormar H, Norrby E (1987) Fuzzy material surrounding measles virus nucleocapsids identified as matrix protein. Arch Virol 94:163–168
Brown HR, Goller NL, Thormar H, Rudelli R, Tourtellotte WW, Shapshak P, Boostanfar R, Wisniewski HM (1987) Measles virus matrix protein gene expression in a subacute sclerosing panencephalitis patient brain and virus isolate demonstrated by cDNA hybridization and immunocytochemistry. Acta Neuropathol (Berl) 75:123–130
Campbell RSF (1957) Encephalitis in canine distemper. Br Vet J 113:143–162
Cattaneo R, Schmid A, Rebmann G, Baczko K, Ter Meulen V, Bellini WJ, Rozenblatt S, Billeter MA (1986) Accumulated measles virus mutations in a case of subacute sclerosing panencephalitis: interrupted matrix protein reading frame and transcription alteration. Virology 154:97–107
Cook SD, Blumberg B, Dowling PC, Deans W, Cross R (1987) Multiple sclerosis and canine distemper on Key West, Florida. Lancet 1:1426–1427
Diallo A (1990) Morbillivirus group: genome organisation and proteins. Vet Microbiol 23:155–163
Dubois-Dalcq MD, Barbosa LH, Hamilton R, Sever JL (1974) Comparison between productive and latent subacute sclerosing panencephalitis viral infection in vitro. Lab Invest 30:241–250
Faaberg KS, Peeples ME (1988) Strain variation and nuclear association of Newcastle disease virus matrix protein. J Virol 62:586–593
Giraudon P, Gerald C, Wild TF (1984) A study of measles virus antigens in acutely and persistently infected cells using monoclonal antibodies: differences in the accumulation of certain viral proteins. Intervirology 21:110–120
Glaus T, Griot C, Richard A, Althaus U, Herschkowitz N, Vandevelde M (1990) Ultrastructural and biochemical findings in brain cell cultures infected with canine distemper virus. Acta Neuropathol 80:59–67
Gordon MT, Anderson DC, Sharpe PT (1991) Canine distemper virus localised in bone cells of patients with Paget's disease. Bone 12:195–201
Griot C, 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
Hamburger D, Griot C, Zurbriggen A, Örvell C, Vandevelde M (1991) Loss of virulence of canine distemper virus is associated with a structural change recognized by a monoclonal antibody. Experientia 47:842–845
Ho CK, Babiuk LA (1979) II. Role of antibody in antigen modulation and prevention of intercellular and extracellular spread of canine distemper virus. Immunology 38:765–772
Kimoto T (1986) In vitro and in vivo properties the virus causing natural canine distemper encephalitis. J Gen Virol 67:487–503
Kingsbury DW (1990) Paramyxoviridae and their replication. In: Fields BN, Knipe DM et al (eds) Virology, 2nd edn. Raven Press, New York, pp 945–962
Koestner A (1975) Distemper-associated demyelinating encephalomyelitis. Am J Pathol 78:361–364
Koestner A, Long JF (1970) Ultrastructure of canine distemper virus in explant tissue cultures of canine cerebellum. Lab Invest 23:196–201
Krakowka S, Koestner A (1976) Age-related susceptibility to infection with canine distemper virus in gnotobiotic dogs. J Infect Dis 134:629–632
Krakowka S, Olsen R, Confer A, Koestner A, McCullough B (1975) Serologic response to canine distemper viral antigens in gnotobiotic dogs infected with canine distemper virus. J Infect Dis 132:384–392
Krakowka S, Axthelm MK, Johnson GC (1985) Canine distemper virus. In: Olsen RG, Krakowka S, Blakeslee JR (eds) Comparative pathobiology of viral diseases, vol 2. CRC Press, Boca Raton, pp 137–164
Liebert UG, Baczko K, Budka H, Ter Meulen V (1986) Restricted expression of measles virus proteins in brains from cases of subacute sclerosing panencephalitis. J Gen Virol 67:2435–2444
Liebert UG, Schneider-Schaulies S, Baczko K, Ter Meulen V (1990) Antibody-induced restriction of viral gene expression in measles encephalitis in rats. J Virol 64:706–713
Mitchell WJ, Summers BA, Appel MJG (1991) Viral expression in experimental canine distemper demyelinating encephalitis. J Comp Pathol 104:77–87
Norrby E, Kristensson K, Brzosko WJ, Kapsenberg JG (1985) Measles virus matrix protein detected by immune fluorescence with monoclonal antibodies in the brain of patients with subacute sclerosing panencephalitis. J Virol 56:337–340
Örvell C (1980) Structural polypeptides of canine distemper virus. Arch Virol 66:193–206
Örvell C, Sheshberadaran H, Norrby E (1985) Preparation and characterization of monoclonal antibodies directed against four structural components of canine distemper virus. J Gen Virol 66:443–456
Patterson S, Gross J, Oxford JS (1988) The intracellular distribution of influenza virus matrix protein and nucleoprotein in infected cells and their relationship to haemagglutinin in the plasma membrane. J Gen Virol 69:1859–1872
Raw ME, Pearson GR, Brown PJ, Baumgärtner W (1992) Canine distemper infection associated with acute nervous signs in dogs. Vet Rec 130:291–293
Rima BK, Duffy N, Mitchell WJ, Summers BA, Appel MJG (1991) Correlation between humoral immune responses and presence of virus in the CNS in dogs experimentally infected with canine distemper virus. Arch Virol 121:1–8
Schneider-Schaulies S, Liebert UG, Baczko K, Cattaneo B, Billeter M, Ter Meulen V (1989) Restriction of measles virus gene expression in acute and subacute encephalitis of Lewis rats. Virology 171:525–534
Sheshberadaran H, Norrby E (1984) Three monoclonal antibodies against measles virus F protein cross-react with cellular stress proteins. J Virol 52:995–999
Summers BA, Greisen HA, Appel MJG (1978) Possible initiation of viral encephalomyelitis in dogs by migrating lymphocytes infected with distemper virus. Lancet II:187–189
Summers BA, Greisen HA, Appel MJG (1984) Canine distemper encephalomyelitis: variation with virus strain. J Comp Pathol 94:65–75
Tyrrell DLJ, Rafter DJ, Örvell C, Norrby E (1980) Isolation and immunological characterization of the nucleocapsid and membrane proteins of measles virus. J Gen Virol 51:307–315
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
Vandevelde M, Zurbriggen A, Steck A, Bichsel P (1986) Studies on the intrathecal humoral immune response on canine distemper encephalitis. J Neuroimmunol 11:41–51
Vollmer TL, Waxman SG (1991) Multiple sclerosis and other demyelinating disorders. In: Rosenberg RN (ed) Comprehensive Neurology. Raven Press, New York, pp 489–523
Wechsler SL, Fields BN (1978) Intracellular synthesis of measles virus-specified polypeptides. J Virol 25:285–297
Zinnheimer-Dreikorn J, Koschel KP (1990) Antigenic modulation of measles subacute sclerosing panencephalitis virus in a persistently infected rat glioma cell line by monoclonal anti-haemagglutinin antibodies. J Gen Virol 71:1391–1394
Zurbriggen A, Vandevelde M, Dumas M (1986) Secondary degeneration of oligodendrocytes in canine distemper virus infection in vitro. Lab Invest 54:424–431
Author information
Authors and Affiliations
Additional information
Supported by the Gemeinnützige Hertie-Stiftung (grant no. GHS 203/91)
Rights and permissions
About this article
Cite this article
Alldinger, S., Baumgärtner, W. & Örvell, C. Restricted expression of viral surface proteins in canine distemper encephalitis. Acta Neuropathol 85, 635–645 (1993). https://doi.org/10.1007/BF00334674
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00334674