Background Paper On the Role of the Immune Response in the Course of Coronavirus JHM-Induced Encephalomyelitides in Mice and Rats

  • Rüdiger Dörries
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 276)


Virus infections of the central nervous system (CNS) may result in the loss of myelin sheaths without axonal destruction. Severe neurological symptoms occur as a consequence of this phenomenon which is called primary demyelination. The sequence of events leading to primary demyelination during the course of viral infections of the CNS is only partially understood. Although it is well established that cytolytic infection of the Oligodendroglia cell can cause primary demyelination, mononuclear infiltrates in subacute and chronic courses of the disease indicate that immunological events may take part in this process (reviewed by Johnson (1)). For several reasons, investigations into the dynamic interactions between virus infection of the CNS and the local immune response cannot be conducted in man. (1) Usually clinical specimens are restricted to cerebrospinal fluid which gives limited information about pathological events occuring in the brain parenchyma (2). It is not known at which time point of the preceeding systemic infection, the virus enters the brain and biopsies are taken too rarely and infrequently to understand the kinetics of the events (3). The general absence of genetic homogeneity in man complicates attempts to detect the influence of the immunogenetic background on the course of the disease. In contrast, intracerebral infections of rodents with the murine hepatitis virus JHM (MHV-4) are excellent models to study the relationships between virus-induced demyelination and the local immune response. Based on the work of Cheever (2), animal models of JHM virus-induced demyelinating encephalomyelitis have been developed in mice as well as in rats (3–5). In recent years striking similarities in the course of the infection in both rodents have been detected which might give the impression that these two models can substitute for each other. However, subtle but important differences do exist. Therefore, in the present review attempts are made to summarize and compare the knowledge about demyelinating encephalomyelitides in rats and mice, giving emphasis to the role of the local immune response in the brain.


Grey Matter Demyelinating Disease Local Immune Response Mouse Hepatitis Virus Murine Hepatitis Virus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    R. T. Johnson, Chronic inflammatory and demyelinating diseases, In: “Viral infections of the Nervous System,” R. T. Johnson, ed., Raven Press, New York, (1982).Google Scholar
  2. 2.
    F. S. Cheever, J. B. Daniels, A. M. Pappenheimer, and O. T. Bailey, A murine virus (JHM) causing disseminated encephalomyelitis with extensive destruction of myelin, J. Exp. Med. 90:181(1949).PubMedCrossRefGoogle Scholar
  3. 3.
    L. P. Weiner, Pathogenesis of demyelination induced by a mouse hepatitis virus, Arch. Neurol. 28:298 (1973)PubMedCrossRefGoogle Scholar
  4. 4.
    K. Nagashima, H . Wege, R . Meyermann, and V . der Meulen, Coronavirus-induced subacute demyelinating encephalomyelitis in rats. A morphological analysis, Acta Neuropathol 44: 63 (1978)PubMedCrossRefGoogle Scholar
  5. 5.
    O. Sorensen, D. Perry, and S. Dales, In vivo and in vitro models of demyelinating diseases. III. JHM virus infection of rats. Arch. Neurol. 37: 478 (1980)PubMedCrossRefGoogle Scholar
  6. 6.
    R. M. Herndon, D. E. Griffin, U. McCormick, and L. P. Weiner, Mouse hepatitis virus- induced recurrent demyelination, Arch. Neurol. 32: 32 (1975)PubMedCrossRefGoogle Scholar
  7. 8.
    M. Koga, H. Wege, and V. der Meulen, Sequence of murine Coronavirus JHM-induced neuropathological changes in rats, Neuropathol. Appl. Neurobiol. 10 :173 (1984)PubMedCrossRefGoogle Scholar
  8. 9.
    R. Watanabe, H. Wege, and V. ter Meulen, Comparative analysis of Coronavirus JHM- induced demyelinating encephalomyelitis in Lewis and Brown Norway rats, Lab . Invest. 57: 375 (1987)PubMedGoogle Scholar
  9. 10.
    S. A . Stohlman, and L. P. Weiner, Chronic central nervous system demyelination in mice after JHM virus infection, Neurology 31:38 (1981)PubMedGoogle Scholar
  10. 11.
    R. L. Knobler, M. V. Haspel, and M. B. A. Oldstone, Mouse hepatitis virus type 4 (JHM strain) -induced fatal central nervous system disease. I. Genetic control and the murine neuron as the susceptible site of the disease, J. Exp . Med .153: 832 (1981)PubMedCrossRefGoogle Scholar
  11. 12.
    A. R. Collins, L. A. Tunison, and R. L. Knobler, Mouse hepatitis virus type 4 infection of primary glial cultures from genetically sysceptible and resistant mice, Infec . Immun. 40: 1192 (1983)Google Scholar
  12. 13.
    Beushausen, and S. Dales, In vivo and in vitro models of demyelinating diseases. XI. Tropism and differentiation regulate the infectious process of coronaviruses in primary explants of the rat CNS, Virology 141: 89 (1985)PubMedCrossRefGoogle Scholar
  13. 14.
    O. Sorensen, R. Dugre, D. Percy, and S. Dales, In vivo and in vitro models of demyelinating disease: Endogenous factors influencing demyelinating disease caused by mouse hepatitis virus in rats and mice, Infec. Immun. 37: 1248 (1982)Google Scholar
  14. 15.
    M. J. Zimmer, and S. Dales, In vivo and In vitro models of demyelinating diseases. XXIV. The infectious process in cyclosporin A-treated Wistar Lewis rats inoculated with JHM virus, Microb. Pathogen. 6: 7 (1989)CrossRefGoogle Scholar
  15. 16.
    S. Perlman, R. Schelper, E. Bolger, and D. Ries, Late onset, symptomatic, demyelinating encephalomyelitis in mice infected with MHV-JHM in the presence of maternal antibody, Microb. Pathogen. 2: 185 (1987)CrossRefGoogle Scholar
  16. 17.
    H. Wege, R. Watanabe, M. Koga and V. der Meulen, Coronavirus JHM-induced demyelinating encephalomyelitis in rats: Influence of immunity on the course of disease, in: “Immunology of Nervous System Infections, Progress in Brain Research, Vol. 59,” P. 0. Behan, V. ter Meulen, and F. Clifford Rose, eds., Elsevier Science Publishers, New York, (1983).Google Scholar
  17. 18.
    J. O. Fleming, M. D. Trousdale, J. Bradbury, S. A. Stohlman, and L.P. Weiner, Experimental demyelination induced by Coronavirus JHM (MHV-4): molecular identification of a viral determinant of paralytic disease, Microb. Pathogen. 3: 9 (1987).CrossRefGoogle Scholar
  18. 19.
    M. J. Buchmeier, R. G. Dalziel, and M. J. M. Koolen, Coronavirus-induced CNS disease: a model for virus-induced demyelination, J. Neuroimmunol. 20: 111 (1988)PubMedCrossRefGoogle Scholar
  19. 20.
    H. Wege, J. Winter, P. Massa, R. Dömes, and V. der Meulen, Coronavirus JHM-induced demyelinating disease: Specific domains on the E2-protein are associated with neurovirolence, in: “Coronaviruses. Advances in Experimental Medicine and Biology, Vol. 218,” M. C. Lai, and S. A. Stohlman, eds., Plenum Publishing Corporation, New York, (1987).Google Scholar
  20. 21.
    M. J. Buchmeier, H. A. Lewicki, P. J. Talbot, and R. L. Knobler, Murine hepatitis virus- 4 (strain JHM)-induced neurological disease is modulated in vivo by monoclonal antibody, Virologv 132: 261 (1984).CrossRefGoogle Scholar
  21. 22.
    M. V. Haspel, P. W. Lampert, and M. B. A. Oldstone, Temperature sensitive mutants of mouse hepatitis virus produce a high incidence of demyelination, Proc. Natl. AcadSci. USA 75: 4033 (1978)PubMedCrossRefGoogle Scholar
  22. 23.
    R. L. Knobler, M. Dubois-Dalcq, M. V. Haspel, A. P. Claysmith, P. W. Lampert, and M. B. A. Oldstone, Selective localization of wild type and mutant mouse hepatitis virus (JHM strain) antigens in CNS tissue by fluorescence, light and electron microscopy, J. Neuroimmunol. 1: 81 (1981)PubMedCrossRefGoogle Scholar
  23. 24.
    H. Wege, M. Koga, R. Watanabe, K. Nagashima, and V. ter Meulen, Neurovirulence of murine Coronavirus JHM temperature-sensitive mutants in rats, Infec. Immun. 39: 1316(1983)Google Scholar
  24. 25.
    J. G. Woodward, G. Matsushima, J. A. Frelinger, and S. A. Stohlman, Production and characterization of T cell clones specific for mouse hepatitis virus, strain JHM: In vivo and in vitro analysis, J. Immunol. 133: 1016 (1984).PubMedGoogle Scholar
  25. 26.
    S. A. Stohlman, G. K. Matsushima, N. Castell, and L. P. Weiner, In vivo effects of coronavirus-specific T cell clones: DTH inducer cells prevent a lethal infection, but do not inhibit virus replication, J. Immunol. 136: 3052 (1986).PubMedGoogle Scholar
  26. 27.
    S. A. Stohlman, M. A. Sussman, G. K. Matsushima, R. A. Shubin andS. S. Erlich, Delayed-type hypersensitivity response in the central nervous system during JHM virus infection requires viral specificity for protection, J. Neuroimmunol. 19: 255 (1988)PubMedCrossRefGoogle Scholar
  27. 28.
    S. S. Erlich, G. K. Matsushima, and S. A. Stohlman, Studies on the mechanism of protection from acute viral encephalomyelitis by delayed-type hypersensitivity inducer T cell clones, J. Neurol. Sci. 90: 203 (1989).PubMedCrossRefGoogle Scholar
  28. 29.
    M. A. Sussman, R. A. Shubin, S. Kyuwa, and S. A. Stohlman, T-cell-mediated clearance of mouse hepatitis virus strain JHM from the central nervous system, J. Virol. 63: 3051 (1989).PubMedGoogle Scholar
  29. 30.
    O. Sorensen, A. Saravani, and S. Dales, In vivo and in vitro models of \demyelinating disease, XXIII: Infection by JHM virus of athymic rats, in: “Coronaviruses. Advances in Experimental Medicine and Biology, Vol. 218, M. C. Lai, and S. A. Stohlman, eds., Plenum Publishing Corporation, New York, (1987).Google Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Rüdiger Dörries
    • 1
  1. 1.Institut für Virologie und Immunbiologie der ÜniversitätWürzburgFed. Rep. Germany

Personalised recommendations