Coronaviruses pp 307-320 | Cite as

Coronavirus JHM Induced Demyelinating Disease: Specific Domains on the E2-Protein are Associated with Neurovirulence

  • H. Wege
  • J. Winter
  • P. Massa
  • R. Dörries
  • V. ter Meulen
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 218)


Infections of mice and rats with the coronavirus JHM are well established model systems to study mechanisms of virus in-duced demyelination9, 11, 13–15, 20–22, Massa et al., Dörries et al. this volume). Using virus strains originating from similar sources highly variable or even contradictory observations were made with regard to neurovirulence, type of disease and tropism for glial cells2, 3, 12. Despite of the highly advanced knowledge of virus structure at the molecular level the mechanisms of virus-host interactions important for pathogenesis are largely unknown. It had been shown previously, that intracerebral infection of Lewis rats can lead to encephalomyelitides associated with variable clinical symptoms and inflammatory demyelination. In most cases a rapidly progressing, fatal acute disease develops within 8–12 days p. i. (AE). Most interesting for studies of virus induced demyelination are animals, which show a slower onset of clinical signs (e. g. ataxic gait, paralysis) after incubation times of several weeks to months13, 14, 15. Such animals often survive, can suffer from clinical signs for months or sometimes develop a relapse21.


Acute Hepatitis Cell Fusion Mouse Hepatitis Virus Murine Hepatitis Virus Murine Coronavirus 
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.
    H.M. Baybutt, H. Wege, M.J. Carter, and V. ter Meulen, Adaptation of coronavirus JHM to persistent infection of murine Sac(−) cells. J Gen Virol 65: 915 (1984).PubMedCrossRefGoogle Scholar
  2. 2.
    M.F. van Berlo, G. Wolswijk, J. Calafat, M.J.M. Koolen, M.C. Horzinek, and B.A.M. van der Zeijst, Restricted replication of mouse hepatitis virus A59 in primary mouse brain astrocytes correlates with reduced pathogenicity. J Virol 58: 426 (1986).PubMedGoogle Scholar
  3. 3.
    S. Beushausen, and S. Dales, In vivo and in vitro models of demyelinating disease. XI. Tropism and differentiation regulate the infectious process of coronaviruses in primary expiants of the rat CNS. Virology 141: 89 (1985).PubMedCrossRefGoogle Scholar
  4. 4.
    R.G. Dalziel, P.W. Lampert, P.J. Talbot, and M.J. Buchmeier, Site-Specific alteration of murine hepatitis virus type 4 peplomer glycoprotein E2 results in reduced neuro-virulence. J Virol 59: 463 (1986).PubMedGoogle Scholar
  5. 5.
    J.O. Fleming, S.A. Stohlman, R.C. Harmon, M.M.C. Lai, J.A. Frelinger, and L.P. Weiner, Antigenic relationships of murine coronaviruses: analysis using monoclonal antibodies to JHM (MHV-4) virus. Virology 131: 296 (1983).PubMedCrossRefGoogle Scholar
  6. 6.
    J.O. Fleming, M.D. Trousdale, F.A.K. El-Zaatari, S.A. Stohlman, and L.P. Weiner, Pathogenicity of antigenic variants of murine coronavirus JHM selected with monoclonal antibodies. J Virol 58: 869 (1986).PubMedGoogle Scholar
  7. 7.
    M.F. Frana, J.N. Behnke, L.S. Sturman, and K.V. Holmes, Proteolytic cleavage of the E2 glycoprotein of murine coronavirus: Host-dependent differences in proteolytic cleavage and cell fusion. J Virol 56: 912 (1985).PubMedGoogle Scholar
  8. 8.
    G. Jiménez, I. Correa, M.P. Melgosa, M.J. Bullido, and M. Enjuanes, Critical epitopes in transmissible gastroenteritis virus neutralization. J Virol 60: 131 (1986).PubMedGoogle Scholar
  9. 9.
    R.L. Knobler, P.W. Lampert, and M.B.A. Oldstone, Virus persistence and recurring demyelination produced by a temperature-sensitive mutant of MHV-4. Nature 298: 279 (1982).PubMedCrossRefGoogle Scholar
  10. 10.
    H. Laude, J.M. Chapsal, J. Gelfi, S. Labiau, and J. Grosclaude, Antigenic structure of transmissible gastroenteritis virus. I. Properties of monoclonal antibodies directed against virion proteins. J gen Virol 67: 119 (1986).PubMedCrossRefGoogle Scholar
  11. 11.
    E. Lavi, D.H. Gilden, Z. Wroblewska, L.B. Rorke, S.R. Weiss, Experimental demyelination produced by the A59 strain of mouse hepatitis virus. Neurology 34: 597 (1984).PubMedCrossRefGoogle Scholar
  12. 12.
    P.T. Massa, H. Wege, and V. ter Meulen, Analysis of murine hepatitis virus (JHM strain) tropism toward Lewis rat glial cells in vitro: Type I astrocytes and brain macrophages (microglia) as primary glial cell targets. Lab Invest 55: 318 (1986).PubMedGoogle Scholar
  13. 13.
    K. Nagashima, H. Wege, R. Meyermann, and V. ter Meulen, Corona virus induced subacute demyelinating encephalomyelitis in rat: a morphological analysis. Acta Neuropathol 44: 63 (1978).PubMedCrossRefGoogle Scholar
  14. 14.
    K. Nagashima, H. Wege, R. Meyermann, and V. ter Meulen, Demyelinating encephalomyelitis induced by a long-term coronavirus infection in rats. Acta Neuropathol 45: 205 (1979).PubMedCrossRefGoogle Scholar
  15. 15.
    O. Sörensen, D. Perry, S. Dales, In vivo and in vitro models of demyelinating diseases. III. JHM infection of rats. Arch Neurol 37: 478 (1980).PubMedCrossRefGoogle Scholar
  16. 16.
    L.S. Sturman, C.S. Ricard, and K.V. Holmes, Proteolytic cleavage of the E2 glycoprotein of murine coronavirus: activation of cell-fusing activity of virions by trypsin and separation of two different 90K cleavage fragments. J Virol 56: 904 (1985).PubMedGoogle Scholar
  17. 17.
    F. Taguchi, S.G. Siddell, H. Wege, and V. ter Meulen, Characterization of a variant virus selected in rat brains after infection by coronavirus mouse hepatitis virus JHM. J Virol 54: 429 (1985).PubMedGoogle Scholar
  18. 18.
    P.J. Talbot, and M.J. Buchmeier, Antigenic variation among murine coronaviruses: Evidence for polymorphism on the peplomer glycoprotein, E2. Virus Res 2: 317 (1985).CrossRefGoogle Scholar
  19. 19.
    P.J. Talbot, A.A. Salmi, R.L. Knobler, and M.J. Buchmeier, Topographical mapping of epitopes on the glycoproteins of murine hepatitis virus-4 (strain JHM): Correlation with biological activities. Virology 132: 250 (1984).PubMedCrossRefGoogle Scholar
  20. 20.
    R. Watanabe, H. Wege, and V. ter Meulen, Adoptive transfer of EAE-like lesions from rats with coronavirus-induced demyelinating encephalomyelitis. Nature 305: 150 (1983).PubMedCrossRefGoogle Scholar
  21. 21.
    H. Wege, R. Watanabe, and V. ter Meulen, Relapsing sub-acute demyelinating encephalomyelitis in rats during the course of coronavirus JHM infection. J. Neuroimmunol 6: 325 (1984).PubMedCrossRefGoogle Scholar
  22. 22.
    H. Wege, P.T. Massa, R. Dörries, R. Watanabe, and V. ter Meulen, Coronavirus infection of rats: a model for virus induced demyelinating disease associated with autoimmunity, in: Modern Trends in Virology (Bauer et al., eds., Springer Verlag (1986) (in press).Google Scholar
  23. 23.
    H. Wege, R. Dörries, and H. Wege, Hybridoma antibodies to the murine coronavirus JHM: characterization of epitopes on the peplomer protein (E2). J Gen Virol 65: 1931 (1984).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • H. Wege
    • 1
  • J. Winter
    • 1
  • P. Massa
    • 1
  • R. Dörries
    • 1
  • V. ter Meulen
    • 1
  1. 1.Institute of Virology and ImmunobiologyUniversity of WürzburgWürzburgGermany

Personalised recommendations