Coronavirus Induced Demyelinating Encephalomyelitis in Rats: Immunopathological Aspects of Viral Persistency

  • Helmut Wege
  • Jörn Winter
  • Heiner Körner
  • Egbert Flory
  • Fritz Zimprich
  • Hans Lassmann
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 276)


Lesions of primary demyelination are a characteristic neuro-pathological finding for several important neurological diseases of humans and animals. Such diseases can be caused by virus infections like measles, herpes or distemper. In multiple sclerosis, a disease with unknown etiology, a viral agent could be a trigger factor23. Coronavirus infections of rodents are studied as interesting experimental models to investigate mechanisms of virus induced demyelination19.


Infectious Virus Spike Protein Murine Hepatitis Virus Coronavirus Infection Acta Neuropath 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Buchmeier, M.J., Lewicki, H.A., Talbot, P.J., Knobler, R.L. Murine hepatitis virus-4 (strain JHM)-induced neurologic disease is modulated in vivo by monoclonal antibody. Virol. 132, 261–270 (1984).CrossRefGoogle Scholar
  2. 2.
    Dalziel, R.G., Lampert, P.W., Talbot, P.J., Buchmeier, M.J. Site-Specific alteration of murine hepatitis virus type 4 peplomer glycoprotein E2 results in reduced neurovirulence. J. Virol. £2, 463–471 (1986).Google Scholar
  3. 3.
    Dörries, R., Watanabe, R., Wege, H., ter Meulen, V. Murine Coronavirus induced encephalomyelitides in rats: Analysis of immunoglobulins and virus-specific antibodies in serum and cerebrospinal fluid. J. Neuroimmunol. 12, 131–142 (1986).PubMedCrossRefGoogle Scholar
  4. 4.
    Fleming, J.O., Trousdale, M.D., Bradbury, J., Stohlman, S.A., Weiner, L.P. Experimental demyelination induced by Coronavirus JHM (MHV-4): Molecular identification of a viral determinant of paralytic disease. Microbial Pathogenesis 3 ,9–20 (1987) .PubMedCrossRefGoogle Scholar
  5. 5.
    Fujinami, R.S, Oldstone, M.B.A. Antibody initiates virus persistence: Immune modulation and measles virus infection. In: Notkins, A.L. and Oldstone, M.B.A. (ed). Concepts in viral path. Springer Verlag 1986Google Scholar
  6. 6.
    Lassmann, H., Brunner, C., Bradl, M., Linington, C. Experimental allergic encephalomyelitis: the balance between encephalitogenic T lymphocytes and demyelinating antibodies determines size and structure of demyelinated lesions. Acta Neuropathol. (Berl.) 75 ,566–576 (1988)CrossRefGoogle Scholar
  7. 7.
    Massa, P. T., Dörries, R., ter Meulen, V. Viral Particles induce Ia Antigen Expression on Astrocytes. Nature 320, 543–546 (1986).PubMedCrossRefGoogle Scholar
  8. 8.
    Massa, P.T., Wege, H., ter Meulen, V. Analysis of murine hepatitis virus (JHM strain) tropism toward Lewis rat glial cells in vitro: type I astrocytes and brain macrophages (microglia) are the primary glial cell targets. 55 ,318–327 (1986) .Google Scholar
  9. 9.
    Massa, P. T., Wege, H., ter Meulen, V. Growth pattern of various JHM Coronavirus isolates in primary rat glial cell cultures correlates with differing neurotropism in vivo. Virus Res. 9, 133–144 (1988).PubMedCrossRefGoogle Scholar
  10. 10.
    Morris, V.L., Tieszer, C., Mackinnon, J., Percy, D. Characterization of Coronavirus JHM variants isolated from Wistar Furth rats with a viral-induced demyelinating disease. Virology 169 ,127–136 (1989)PubMedCrossRefGoogle Scholar
  11. 11.
    Nagashima, K., Wege, H., Meyermann, R., ter Meulen, V. Coronavirus induced subacute demyelinating encephalomyelitis in rats. A morphological analysis. Acta Neuropath. 44 ,63–70 (1978) .PubMedCrossRefGoogle Scholar
  12. 12.
    Nagashima, K., Wege, H., Meyermann, R., ter Meulen, V. Demyelinating encephalomyelitis induced by a long-term corona virus infection in rats. Acta Neuropath. 45, 205–213 (1979).PubMedCrossRefGoogle Scholar
  13. 13.
    Perlman, S., Schelper, R., Bolger, E., Ries, S. Late onset, symptomatic, demyelinating encephalomyelitis in mice infected with MHV-JHM in the presence of maternal antibody. Microbial Pathogen. 2, 185–194 (1987).CrossRefGoogle Scholar
  14. 14.
    Stohlman, S.A., Matsushima, G.K., Casteel, N., Weiner, L.P. 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, 8, 3052–3056 (1986).PubMedGoogle Scholar
  15. 15.
    Suzumura, A., Lavi, E., Weiss, S.R., Silberberg, D.H. Coronavirus infection induces H-2 antigen expression on oligodendrocytes and astrocytes. Science 22Z ,991–993 (1986) .CrossRefGoogle Scholar
  16. 16.
    Taguchi, F., Siddell, S.G., Wege, H., ter Meulen, V. Characterization of a variant virus selected in rat brain after infection by murine Coronavirus MHV-JHM. J. Virol. 54, 429–435 (1985).PubMedGoogle Scholar
  17. 17.
    Watanabe, R., Wege, H., ter Meulen, V. Comparative analysis of Coronavirus JHM induced demyelinating encephalomyelitis in Lewis and Brown-Norway rats. Lab. Invest. 57, 375–384 (1987).PubMedGoogle Scholar
  18. 18.
    Watanabe, R., Wege, H., ter Meulen, V. Adoptive transfer of EAE-like lesions by BMP stimulated lymphocytes from rats with coronavirus-induced demyelinating encephalomyelitis. Nature 305, 150–153 (1983).PubMedCrossRefGoogle Scholar
  19. 19.
    Wege, H., Dörries, R., Massa, P., Watanabe, R. Autoimmunity and immune pathological aspects of virus disease. In: Perspectives on autoimmunity I.R. Cohen (ed.). CRC Press, Inc. Boca Raton, Florida (1988) .Google Scholar
  20. 20.
    Wege, H., Dörries, R., Wege, H. Hybridoma antibodies to the murine Coronavirus JHM: Characterisation of Epitopes on the Peplomer protein (E2). J. gen. Virol. 65, 1931–1942 (1984).PubMedCrossRefGoogle Scholar
  21. 21.
    Wege, H., Watanabe, R., ter Meulen, V. Relapsing subacute demyelinating encephalomyelitis in rats in the course of Coronavirus JHM infection. J. Neuroimmunol. 6, 325–336 (1984) .PubMedCrossRefGoogle Scholar
  22. 22.
    Wege, H., Winter, J., Meyermann, R. the Peplomer protein E2 of Coronavirus JHM as a determinant of neurovirulence: Definition of critical epitopes by variant-analysis. J. gen. Virol. 69, 87–98 (1988) .PubMedCrossRefGoogle Scholar
  23. 23.
    Wisniewski, H.M., Schuller-Levis, G.B., Mehta, P.D., Madrid, .E., Lassmann, H. Pathogenetic aspects of multiple sclerosis and experimental models of inflammatory demyelination. Concepts Immunopathol. 2, 128–150 (1985).PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Helmut Wege
  • Jörn Winter
  • Heiner Körner
  • Egbert Flory
    • 1
  • Fritz Zimprich
  • Hans Lassmann
    • 2
  1. 1.Institute for Virology and ImmunbiologyUniversity of WürzburgWürzburgWest Germany
  2. 2.Institute for NeurologyUniversity of ViennaAustria

Personalised recommendations