1887

Abstract

The neurotropic mouse hepatitis virus MHV-JHM induces central nervous system (CNS) demyelination in Lewis rats that pathologically resembles CNS lesions in multiple sclerosis. The mechanisms of MHV-JHM-induced demyelination remain unclear and several studies have implicated the role of the immune response in this process. We have shown previously that protective immunity against MHV-JHM-induced encephalomyelitis was induced by immunization with a vaccinia virus (VV) recombinant expressing MHV-JHM S-protein (VV-S). Here, we present evidence that the time of MHV-JHM challenge after immunization with VV-S plays a critical role in protective immunity. The induction of virus-neutralizing S-protein-specific antibodies prior to the MHV-JHM challenge modulates the disease process and a subacute encephalomyelitis based on a persistent virus infection developed. Typical pathological alterations were lesions of inflammatory demyelination. In addition, the results indicate that after seroconversion, CD8 T cells were no longer essential for virus elimination in contrast to their role in protection during acute encephalomyelitis.

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1995-04-01
2024-11-03
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References

  1. Barrett N., Koschel K., Carter M., ter Meulen V. 1985; Effect of measles antibodies on a measles SSPE virus persistently infected C6 rat glioma cell line. Journal of General Virology 66:1411–1421
    [Google Scholar]
  2. Battegay M., Kyburz D., Hengartner H., Zinkernagel R. M. 1993; Enhancement of disease by neutralizing antiviral anti-bodies in the absence of primed antiviral cytotoxic T cells. European Journal of Immunology 23:3236–3241
    [Google Scholar]
  3. Bergmann C., McMillan M., Stohlman S. 1993; Characterization of the Ld-restricted cytotoxic T-lymphocyte epitope in the mouse hepatitis virus nucleocapsid protein. Journal of Virology 67:7041–7049
    [Google Scholar]
  4. Buchmeier M. J., Lewicki H. A., Talbot P. J., Knobler R. L. 1984; Murine hepatitis virus-4 (strain JHM)-induced neurologic disease is modulated in vivo by monoclonal antibody. Virology 132:261–270
    [Google Scholar]
  5. Collins A. R., Knobler R. L., Powell H., Buchmeier M. J. 1982; Monoclonal antibodies to murine hepatitis virus-4 (strain JHM) define the viral glycoprotein responsible for attachment and cell fusion. Virology 119:358–371
    [Google Scholar]
  6. Compton S. R., Barthold S. W., Smith A. L. 1993; The cellular and molecular pathogenesis of coronaviruses. Laboratory Animal Science 43(1):15–28
    [Google Scholar]
  7. Fleming J. O., Trousdale M. D., El-Zaatari F. A., Stohlman S. A., Weiner L. P. 1986; Pathogenicity of antigenic variants of murine coronavirus JHM selected with monoclonal antibodies. Journal of Virology 58:869–875
    [Google Scholar]
  8. Flory E., Pfleiderer M., Stuhler A., Wege H. 1993; Induction of protective immunity against coronavirus-induced encephalomyelitis: evidence for an important role of CD8+ T cells in vivo. European Journal of Immunology 23:1757–1761
    [Google Scholar]
  9. Fujinami R. S., Norrby E., Oldstone M. B. A. 1984; Antigenic modulation induced by monoclonal antibodies: antibodies to measles virus hemagglutinin alter expression of other viral polypeptides in infected cells. Journal of Immunology 132:2618–2621
    [Google Scholar]
  10. Gallagher T. M., Parker S. E., Buchmeier M. J. 1990; Neutralization-resistant variants of a neurotropic coronavirus are generated by deletions within the amino-terminal half of the spike glycoprotein. Journal of Virology 64:731–741
    [Google Scholar]
  11. Gombold J. L., Hingley S. T., Weiss S. R. 1993; Fusion-defective mutants of mouse hepatitis virus A59 contain a mutation in the spike protein cleavage signal. Journal of Virology 67:4504–4512
    [Google Scholar]
  12. Jonjic S., Pavic I., Lucin P., Rukavina D., Koszinowski U. 1990; Efficacious control of cytomegalovirus infection after long-term depletion of CD8+ T lymphocytes. Journal of Virology 64:5457–5464
    [Google Scholar]
  13. Koga M., Wege H., ter Meulen V. 1984; Sequence of murine coronavirus JHM induced CNS changes in rats. Neuropathology and Applied Neurobiology 10:173–184
    [Google Scholar]
  14. Körner H., Schliephake A., Winter J., Zimprich F., Lassmann H., Sedgwick J., Siddell S., Wege H. 1991; Nucleocapsid or spike protein-specific CD4+ T lymphocytes protect against coronavirus-induced encephalomyelitis in the absence of CD8+ T cells. Journal of Immunology 147:2317–2323
    [Google Scholar]
  15. Lai M. M. 1990; Coronavirus: organization, replication and expression of genome. Annual Review of Microbiology 44:303–333
    [Google Scholar]
  16. Lassmann H., Vass K., Brunner C., Seitelberger F. 1986; Characterization of inflammatory infiltrates in experimental allergic encephalomyelitis. Progress in Neuropathology 6:33–62
    [Google Scholar]
  17. Levine B., Hardwick J. M., Trapp B. D., Crawford T. O., Bollinger R. C., Griffin D. E. 1991; Antibody-mediated clearance of alpha virus infection from neurons. Science 254:856–860
    [Google Scholar]
  18. Nagashima K., Wege H., Meyermann R., ter Meulen V. 1978; Coronavirus induced subacute demyelinating encephalomyelitis in rats. A morphological analysis. Acta Neuropathologica 44:63–70
    [Google Scholar]
  19. Oehen S., Waldner H., Kündig T. M., Hengartner H., Zinkernagel R. M. 1992; Antivirally protective cytotoxic T cell memory to lymphocytic choriomeningitis virus is governed by persisting antigen. Journal of Experimental Medicine 176:1273–1281
    [Google Scholar]
  20. Oldstone M. B. A. 1991; Molecular anatomy of viral persistence. Journal of Virology 65:6381–6386
    [Google Scholar]
  21. Perlman S., Schelper R., Bolger E., Ries D. 1987; Late onset, symptomatic, demyelinating encephalomyelitis in mice infected with MHV-JHM in the presence of maternal antibody. Microbial Pathogenesis 2:185–194
    [Google Scholar]
  22. Schwender S., Imrich H., Dörries R. 1991; The pathogenic role of virus-specific antibody-secreting cells in the central nervous system of rats with different susceptibility to coronavirus-induced demyelinating encephalitis. Immunology 74:533–538
    [Google Scholar]
  23. Schwender S., Hein A., Imrich H., Dorries R. 1994; On the role of different lymphocyte subpopulations in the course of coronavirus MHV IV (JHM)-induced encephalitis in Lewis rats. In Coronaviruses: Molecular Biology and Virus-Host Interactions pp 425–430 Edited by Laude H., Vautherot J. F. New York: Plenum Press;
    [Google Scholar]
  24. Shubin R. A., Sussman M. A., Fleming J. O., Stohlman S. A. 1990; Relapsing encephalomyelitis following transfer of partial immunity to JHM virus. Microbial Pathogenesis 8:305–314
    [Google Scholar]
  25. Sorensen O., Percy D., Dales S. 1980; In vivo and in vitro models of demyelinating diseases. III. JHM virus infection of rats. Archives of Neurology 37:478–484
    [Google Scholar]
  26. Sussman M. A., Shubin R. A., Kyuwa S., Stohlman S. A. 1989; T-cell-mediated clearance of mouse hepatitis virus strain JHM from the central nervous system. Journal of Virology 63:3051–3056
    [Google Scholar]
  27. Wang F. I., Stohlman S. A., Fleming J. O. 1990; Demyelination induced by murine hepatitis virus JHM strain (MHV-4) is immunologically mediated. Journal of Neuroimmunology 30:31–41
    [Google Scholar]
  28. Watanabe R., Wege H., ter Meulen V. 1983; Adoptive transfer of EAE-like lesions by BMP stimulated lymphocytes from rats with coronavirus-induced demyelinating encephalomyelitis. Nature 305:150–153
    [Google Scholar]
  29. Wege H., Koga M., Wege H., ter Meulen V. 1981; JHM infections in rats as a model for acute and subacute demyelinating disease. In Biochemistry and Biology of Coronaviruses pp 327–329 Edited by Ter Meulen V., Siddell S., Wege H. New York: Plenum Press;
    [Google Scholar]
  30. Wege H., Dorries R., Wege H. 1984a; Hybridoma antibodies to the murine coronavirus JHM: characterization of epitopes on the peplomer protein (E2). Journal of General Virology 65:1931–1942
    [Google Scholar]
  31. Wege H., Watanabe R., Ter Meulen V. 1984b; Relapsing subacute demyelinating encephalomyelitis in rats in the course of coronavirus JHM infection. Journal of Neuroimmunology 6:325–336
    [Google Scholar]
  32. Wege H., Winter J., Meyermann R. 1988; The peplomer protein E2 of coronavirus JHM as a determinant of neurovirulence: definition of critical epitopes by variant analysis. Journal of General Virology 69:87–98
    [Google Scholar]
  33. Wege H., Winter J., Körner H., Flory E., Zimprich F., Lassmann H. 1990; Coronavirus induced demyelinating encephalomyelitis in rats: immunpathological aspects of viral persistency. In Coronaviruses and Their Diseases pp 637–645 Edited by Cavanagh D., Brown D. New York: Plenum Press;
    [Google Scholar]
  34. Wege H., Schliephake A., Körner H., Flory E., Wege H. 1993; An immunodominant CD4+ T cell site on the nucleocapsid protein of murine coronavirus contributes to protection against encephalomyelitis. Journal of General Virology 74:1287–1294
    [Google Scholar]
  35. Williamson J. S., Stohlman S. A. 1990; Effective clearance of mouse hepatitis virus from the central nervous system requires both CD4+ and CD8+ T cells. Journal of Virology 64:4589–4592
    [Google Scholar]
  36. Zimprich F., Winter J., Wege H., Lassmann H. 1991; Coronavirus induced primary demyelination: indications for the involvement of a humoral immune response. Neuropathology and Applied Neurobiology 17:469–484
    [Google Scholar]
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