1887

Abstract

For most virus infections of the central nervous system (CNS), immune-mediated damage, the route of inoculation and death of infected cells all contribute to the pathology observed. To investigate the role of these factors in early canine distemper neuropathogenesis, we infected ferrets either intranasally or intraperitoneally with the neurovirulent canine distemper virus strain Snyder Hill. Regardless of the route of inoculation, the virus primarily targeted the olfactory bulb, brainstem, hippocampus and cerebellum, whereas only occasional foci were detected in the cortex. The infection led to widespread neuronal loss, which correlated with the clinical signs observed. Increased numbers of activated microglia, reactive gliosis and different pro-inflammatory cytokines were detected in the infected areas, suggesting that the presence and ultimate death of infected cells at early times after infection trigger strong local immune activation, despite the observed systemic immunosuppression.

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2010-04-01
2024-10-10
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References

  1. Acharya, J. N. & Pacheco, V. H.(2008). Neurologic complications of hepatitis C. Neurologist 14, 151–156.[CrossRef] [Google Scholar]
  2. Alldinger, S., Wunschmann, A., Baumgartner, W., Voss, C. & Kremmer, E.(1996). Up-regulation of major histocompatibility complex class II antigen expression in the central nervous system of dogs with spontaneous canine distemper virus encephalitis. Acta Neuropathol 92, 273–280.[CrossRef] [Google Scholar]
  3. Anderson, J. R. & Field, H. J.(1983). The distribution of herpes simplex type 1 antigen in mouse central nervous system after different routes of inoculation. J Neurol Sci 60, 181–195.[CrossRef] [Google Scholar]
  4. Anderson, D. E. & von Messling, V.(2008). Region between the canine distemper virus M and F genes modulates virulence by controlling fusion protein expression. J Virol 82, 10510–10518.[CrossRef] [Google Scholar]
  5. Appel, M. J.(1969). Pathogenesis of canine distemper. Am J Vet Res 30, 1167–1182. [Google Scholar]
  6. Appel, M. J. & Summers, B. A.(1995). Pathogenicity of morbilliviruses for terrestrial carnivores. Vet Microbiol 44, 187–191.[CrossRef] [Google Scholar]
  7. Appel, M. J., Shek, W. R. & Summers, B. A.(1982). Lymphocyte-mediated immune cytotoxicity in dogs infected with virulent canine distemper virus. Infect Immun 37, 592–600. [Google Scholar]
  8. Axthelm, M. K. & Krakowka, S.(1987). Canine distemper virus: the early blood–brain barrier lesion. Acta Neuropathol 75, 27–33.[CrossRef] [Google Scholar]
  9. Baumgartner, W., Orvell, C. & Reinacher, M.(1989). Naturally occurring canine distemper virus encephalitis: distribution and expression of viral polypeptides in nervous tissues. Acta Neuropathol 78, 504–512.[CrossRef] [Google Scholar]
  10. Caignard, G., Guerbois, M., Labernardiere, J. L., Jacob, Y., Jones, L. M., Wild, F., Tangy, F. & Vidalain, P. O.(2007). Measles virus V protein blocks Jak1-mediated phosphorylation of STAT1 to escape IFN-α/β signaling. Virology 368, 351–362.[CrossRef] [Google Scholar]
  11. Chadwick, D. W., Martin, S., Buxton, P. H. & Tomlinson, A. H.(1982). Measles virus and subacute neurological disease: an unusual presentation of measles inclusion body encephalitis. J Neurol Neurosurg Psychiatry 45, 680–684.[CrossRef] [Google Scholar]
  12. Cocks, B. G., Chang, C. C., Carballido, J. M., Yssel, H., de Vries, J. E. & Aversa, G.(1995). A novel receptor involved in T-cell activation. Nature 376, 260–263.[CrossRef] [Google Scholar]
  13. Confer, A. W., Kahn, D. E., Koestner, A. & Krakowka, S.(1975). Biological properties of a canine distemper virus isolate associated with demyelinating encephalomyelitis. Infect Immun 11, 835–844. [Google Scholar]
  14. de Swart, R. L., Ludlow, M., de Witte, L., Yanagi, Y., van Amerongen, G., McQuaid, S., Yuksel, S., Geijtenbeek, T. B., Duprex, W. P. & Osterhaus, A. D.(2007). Predominant infection of CD150+ lymphocytes and dendritic cells during measles virus infection of macaques. PLoS Pathog 3, e178[CrossRef] [Google Scholar]
  15. Frisk, A. L., Baumgartner, W. & Grone, A.(1999). Dominating interleukin-10 mRNA expression induction in cerebrospinal fluid cells of dogs with natural canine distemper virus induced demyelinating and non-demyelinating CNS lesions. J Neuroimmunol 97, 102–109.[CrossRef] [Google Scholar]
  16. Gnann, J. W., Jr(2002). Varicella-zoster virus: atypical presentations and unusual complications. J Infect Dis 186 (Suppl. 1), S91–S98.[CrossRef] [Google Scholar]
  17. Griffin, D. E.(2001). Measles virus. In Fields Virology, 4th edn, pp. 1401–1441. Edited by D. M. Knipe & P. M. Howley. Philadelphia, PA: Lippincott Williams & Wilkins.
  18. Headley, S. A., Soares, I. C. & Graca, D. L.(2001). Glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes in dogs infected with canine distemper virus. J Comp Pathol 125, 90–97.[CrossRef] [Google Scholar]
  19. Higgins, R. J., Krakowka, S. G., Metzler, A. E. & Koestner, A.(1982). Primary demyelination in experimental canine distemper virus induced encephalomyelitis in gnotobiotic dogs. Sequential immunologic and morphologic findings. Acta Neuropathol 58, 1–8.[CrossRef] [Google Scholar]
  20. Kuss, S. K., Etheredge, C. A. & Pfeiffer, J. K.(2008). Multiple host barriers restrict poliovirus trafficking in mice. PLoS Pathog 4, e1000082[CrossRef] [Google Scholar]
  21. Letendre, S. L., Ellis, R. J., Everall, I., Ances, B., Bharti, A. & McCutchan, J. A.(2009). Neurologic complications of HIV disease and their treatment. Top HIV Med 17, 46–56. [Google Scholar]
  22. Martin, A., Staeheli, P. & Schneider, U.(2006). RNA polymerase II-controlled expression of antigenomic RNA enhances the rescue efficacies of two different members of the Mononegavirales independently of the site of viral genome replication. J Virol 80, 5708–5715.[CrossRef] [Google Scholar]
  23. Moss, W. J., Ota, M. O. & Griffin, D. E.(2004). Measles: immune suppression and immune responses. Int J Biochem Cell Biol 36, 1380–1385.[CrossRef] [Google Scholar]
  24. Ohno, S., Ono, N., Takeda, M., Takeuchi, K. & Yanagi, Y.(2004). Dissection of measles virus V protein in relation to its ability to block alpha/beta interferon signal transduction. J Gen Virol 85, 2991–2999.[CrossRef] [Google Scholar]
  25. Palosaari, H., Parisien, J. P., Rodriguez, J. J., Ulane, C. M. & Horvath, C. M.(2003). STAT protein interference and suppression of cytokine signal transduction by measles virus V protein. J Virol 77, 7635–7644.[CrossRef] [Google Scholar]
  26. Rima, B. K., Duffy, N., Mitchell, W. J., Summers, B. A. & Appel, M. J.(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.[CrossRef] [Google Scholar]
  27. Rudd, P. A., Cattaneo, R. & von Messling, V.(2006). Canine distemper virus uses both the anterograde and the hematogenous pathway for neuroinvasion. J Virol 80, 9361–9370.[CrossRef] [Google Scholar]
  28. Sanchez-Lanier, M., Guerin, P., McLaren, L. C. & Bankhurst, A. D.(1988). Measles virus-induced suppression of lymphocyte proliferation. Cell Immunol 116, 367–381.[CrossRef] [Google Scholar]
  29. Schlender, J., Schnorr, J. J., Spielhoffer, P., Cathomen, T., Cattaneo, R., Billeter, M. A., ter Meulen, V. & Schneider-Schaulies, S.(1996). Interaction of measles virus glycoproteins with the surface of uninfected peripheral blood lymphocytes induces immunosuppression in vitro. Proc Natl Acad Sci U S A 93, 13194–13199.[CrossRef] [Google Scholar]
  30. Schneider-Schaulies, J. & Schneider-Schaulies, S.(2008). Receptor interactions, tropism, and mechanisms involved in morbillivirus-induced immunomodulation. Adv Virus Res 71, 173–205. [Google Scholar]
  31. Sidorenko, S. P. & Clark, E. A.(2003). The dual-function CD150 receptor subfamily: the viral attraction. Nat Immunol 4, 19–24.[CrossRef] [Google Scholar]
  32. Sinchaisri, T. A., Nagata, T., Yoshikawa, Y., Kai, C. & Yamanouchi, K.(1992). Immunohistochemical and histopathological study of experimental rabies infection in mice. J Vet Med Sci 54, 409–416.[CrossRef] [Google Scholar]
  33. Stephensen, C. B., Welter, J., Thaker, S. R., Taylor, J., Tartaglia, J. & Paoletti, E.(1997). Canine distemper virus (CDV) infection of ferrets as a model for testing Morbillivirus vaccine strategies: NYVAC- and ALVAC-based CDV recombinants protect against symptomatic infection. J Virol 71, 1506–1513. [Google Scholar]
  34. Stoica, G., Tasca, S. I. & Wong, P. K.(2000). Motor neuronal loss and neurofilament-ubiquitin alteration in MoMuLV-ts1 encephalopathy. Acta Neuropathol 99, 238–244.[CrossRef] [Google Scholar]
  35. Summers, B. A. & Appel, M. J.(1994). Aspects of canine distemper virus and measles virus encephalomyelitis. Neuropathol Appl Neurobiol 20, 525–534.[CrossRef] [Google Scholar]
  36. Summers, B. A., Greisen, H. A. & Appel, M. J.(1984). Canine distemper encephalomyelitis: variation with virus strain. J Comp Pathol 94, 65–75.[CrossRef] [Google Scholar]
  37. Svitek, N. & von Messling, V.(2007). Early cytokine mRNA expression profiles predict Morbillivirus disease outcome in ferrets. Virology 362, 404–410.[CrossRef] [Google Scholar]
  38. Takeuchi, K., Kadota, S. I., Takeda, M., Miyajima, N. & Nagata, K.(2003). Measles virus V protein blocks interferon (IFN)-alpha/beta but not IFN-gamma signaling by inhibiting STAT1 and STAT2 phosphorylation. FEBS Lett 545, 177–182.[CrossRef] [Google Scholar]
  39. Tatsuo, H., Ono, N. & Yanagi, Y.(2001). Morbilliviruses use signaling lymphocyte activation molecules (CD150) as cellular receptors. J Virol 75, 5842–5850.[CrossRef] [Google Scholar]
  40. Tipold, A., Moore, P., Zurbriggen, A., Burgener, I., Barben, G. & Vandevelde, M.(1999). Early T cell response in the central nervous system in canine distemper virus infection. Acta Neuropathol 97, 45–56.[CrossRef] [Google Scholar]
  41. Vandevelde, M. & Zurbriggen, A.(2005). Demyelination in canine distemper virus infection: a review. Acta Neuropathol 109, 56–68.[CrossRef] [Google Scholar]
  42. Vandevelde, M., Zurbriggen, A., Higgins, R. J. & Palmer, D.(1985). Spread and distribution of viral antigen in nervous canine distemper. Acta Neuropathol 67, 211–218.[CrossRef] [Google Scholar]
  43. van Moll, P., Alldinger, S., Baumgartner, W. & Adami, M.(1995). Distemper in wild carnivores: an epidemiological, histological and immunocytochemical study. Vet Microbiol 44, 193–199.[CrossRef] [Google Scholar]
  44. von Messling, V., Springfeld, C., Devaux, P. & Cattaneo, R.(2003). A ferret model of canine distemper virus virulence and immunosuppression. J Virol 77, 12579–12591.[CrossRef] [Google Scholar]
  45. von Messling, V., Milosevic, D. & Cattaneo, R.(2004). Tropism illuminated: lymphocyte-based pathways blazed by lethal morbillivirus through the host immune system. Proc Natl Acad Sci U S A 101, 14216–14221.[CrossRef] [Google Scholar]
  46. von Messling, V., Svitek, N. & Cattaneo, R.(2006). Receptor (SLAM [CD150]) recognition and the V protein sustain swift lymphocyte-based invasion of mucosal tissue and lymphatic organs by a morbillivirus. J Virol 80, 6084–6092.[CrossRef] [Google Scholar]
  47. Whitley, R. J. & Gnann, J. W.(2002). Viral encephalitis: familiar infections and emerging pathogens. Lancet 359, 507–513.[CrossRef] [Google Scholar]
  48. Wunschmann, A., Alldinger, S., Kremmer, E. & Baumgartner, W.(1999). Identification of CD4+ and CD8+ T cell subsets and B cells in the brain of dogs with spontaneous acute, subacute-, and chronic-demyelinating distemper encephalitis. Vet Immunol Immunopathol 67, 101–116.[CrossRef] [Google Scholar]
  49. Zurbriggen, A., Schmid, I., Graber, H. U. & Vandevelde, M.(1998). Oligodendroglial pathology in canine distemper. Acta Neuropathol 95, 71–77.[CrossRef] [Google Scholar]
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