H-2 Antigens pp 747-756 | Cite as

The Contribution of MHC Gene Products to Demyelination by Theiler’s Virus

  • Moses Rodriguez
  • Chella S. David
  • Larry R. Pease
Part of the NATO ASI Series book series (NSSA, volume 144)


Infection with Theiler’s murine encephalomyelitis virus (TMEV) provides an opportunity to study viral persistence and neuropathologic abnormalities in the central nervous system. This picornavirus was first recovered by Max Theiler in 1934 from a mouse suffering from spontaneous flaccid paralysis of the hind legs (Theiler, 1934). The virus is similar in size, virulence, buoyant density and viral structural proteins to poliovirus (Lorch et al., 1981). Early studies showed that intracerebral or intranasal inoculation of the virus into neonatal or weanling mice resulted in spinal cord lesions characterized by neuronal necrosis, especially of anterior horn cells, which is very similar to human poliomyelitis. This virus received little attention until Daniels et al. (1952) described an isolate of TMEV, subsequently designated DA strain, which had the propensity to induce in young adult mice primary demyelination in the central nervous system. The pathology in the spinal cord was characterized by an intense inflammatory infiltrate associated with primary destruction of myelin sheaths with relative preservation of axons (Dal Canto and Lipton, 1975; Lehrich et al., 1976).


Major Histocompatibility Complex Flaccid Paralysis Anterior Horn Cell Pathologic Abnormality Susceptible Mouse 
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  1. Cash, E., Chammoro, M., and Brahic, M., 1985, Theiler’s virus RNA and protein synthesis in the central nervous system of demyelinating mice, Virology, 144: 290.PubMedCrossRefGoogle Scholar
  2. Chamorro, M., Aubert, C., and Brahic, M., 1986, Demyelinating lesions due to Theiler’s virus are associated with ongoing central nervous system infection, J. Virol., 57: 992.PubMedCentralPubMedGoogle Scholar
  3. Clatch, R. J., Melvold, R. W., Miller, S. D., and Lipton, H. L., 1985, Theiler’s murine encephalomyelitis virus (TMEV)-induced demyelinating disease in mice is influenced by the H-2D region: Correlation with TMEV-specific delayed-type hypersensitivity, J. Immunol., 135: 1408.PubMedGoogle Scholar
  4. Clatch, R. J., Lipton, H. L., and Miller, S. D., 1986, Characterization of Theiler’s murine encephalomyelitis virus (TMEV)-specific delayedtype hypersensitivity responses in TMEV-induced demyelinating disease: Correlation with clinical signs, J. Immunol., 136: 920.PubMedGoogle Scholar
  5. Daniels, J. B., Pappenheimer, A. M., and Richardson, S., 1952, Observations on encephalomyelitis of mice (DA strain), J. Exp. Med., 96: 517.PubMedCentralPubMedCrossRefGoogle Scholar
  6. Dal Canto, M. C., and Lipton, H. L., 1975, Primary demyelination in Theiler’s virus infection: An ultrastructual study, Lab. Invest., 33: 626.Google Scholar
  7. Dal Canto, M. C., and Lipton, H. L., 1982, Ultrastructural immunohistochemical localization of virus in acute and chronic demyelinating Theiler’s virus infection, Am. J. Pathol., 106: 20.Google Scholar
  8. Dal Canto, M. C., and Rabinowitz, S. G., 1982a, Experimental models of virus-induced demyelination of the central nervous system, Ann. Neurol., 11: 109.CrossRefGoogle Scholar
  9. Friedmann, A., Frankel, G., Lorch, Y., and Steinman, L., 1987, Monoclonal anti-I-A antibody reverses chronic paralysis and demyelination in Theiler’s virus-infected mice: Critical importance of timing of treatment, J. Virol., 61: 898.PubMedCentralPubMedGoogle Scholar
  10. Lehrich, J. R., Arnason, B. G. W., and Hochberg, F. H., 1976, Demyelinative myelopathy in mice induced by the DA virus, J. Neurol. Sci., 29: 149.PubMedCrossRefGoogle Scholar
  11. Lipton, H. L., 1975, Theiler’s virus infection in mice: An unusual biphasic disease process leading to demyelination, Infect. Immun., 11: 1147.PubMedCentralPubMedGoogle Scholar
  12. Lipton, H. L., and Dal Canto, M. C., 1976, Theiler’s virus-induced demyelination: Prevention by immunosuppression, Science, 192: 62.PubMedCrossRefGoogle Scholar
  13. Lipton, H. L., and Dal Canto, M. C., 1977, Contrasting effects of immunosuppression on Theiler’s virus infection in mice, Infect. Immun., 15: 903.PubMedCentralPubMedGoogle Scholar
  14. Lipton, H. L., and Dal Canto, M. C., 1979, The TO strains of Theiler’s viruses cause “slow virus-like” infections in mice, Ann. Neurol., 6: 25.PubMedCrossRefGoogle Scholar
  15. Lipton, H. L., and Dal Canto, M. C., 1979a, Susceptibility of inbred mice to chronic central nervous system infection by Theiler’s murine encephalomyelitis virus, Infect. Immun., 26: 369.PubMedCentralPubMedGoogle Scholar
  16. Lipton, H. L., and Melvold, R., 1984, Genetic analysis of susceptibility to Theiler’s virus-induced demyelinating disease in mice, J. Immunol., 132: 1821.PubMedGoogle Scholar
  17. Lorch, Y., Friedmann, A., Lipton, H. L., and Kotler, M., 1981, Theiler’s murine encephalomyelitis virus group includes two distinct genetic subgroups that differ pathologically and biologically, J. Virol., 40: 560.PubMedCentralPubMedGoogle Scholar
  18. Rodriguez, M., Leibowitz, J. L., and Lampert, P. W., 1983, Persistent infection of oligodendrocytes in Theiler’s virus-induced encephalomyelitis, Ann. Neurol., 13: 426.PubMedCrossRefGoogle Scholar
  19. Rodriguez, M., Leibowitz, J. L., Powell, H. C., and Lampert, P. W., 1983a, Neonatal infection with the Daniels strain of Theiler’s murine encephalomyelitis virus, Lab. Invest., 49: 672.PubMedGoogle Scholar
  20. Rodriguez, M., 1985, Virus-induced demyelination in mice: “Dying back” of oligodendrocytes, Mayo Clin. Proc., 60: 433.PubMedCrossRefGoogle Scholar
  21. Rodriguez, M., and David, C. S., 1985a, Demyelination Induced by Theiler’s Virus: Influence of the H-2 Haplotype, J. Immunol., 135: 2145.PubMedGoogle Scholar
  22. Rodriguez, M., Lafuse, W., Leibowitz, J., and David, C. S., 1986, Partial suppression of Theiler’s virus-induced demyelination in vivo by administration of monoclonal antibodies to immune response genes products (Ia antigens), Neurol., 36: 964.CrossRefGoogle Scholar
  23. Rodriguez, M., Leibowitz, J., and David, C. S., 1986a, Susceptibility to Theiler’s virus-induced demyelination: Mapping of the gene within the H-2D region, J. Exp. Med., 163: 620.PubMedCrossRefGoogle Scholar
  24. Rodriguez, M., Pease, L. R., and David, C. S., 1986b, Immune-mediated injury of virus-infected oligodendrocytes. A model of multiple sclerosis, Immunol. Today, 7: 359.CrossRefGoogle Scholar
  25. Rodriguez, M., and Quddus, J., 1986c, Effect of cyclosporin A, silica quartz dust and macrophage protease inhibitors in virus-induced demyelination, J. Neuroimmunol., 13: 159.PubMedCrossRefGoogle Scholar
  26. Rodriguez, M., Pierce, M. L., and Howie, E. A., 1987, Immune response gene products (Ia antigens) on glial and endothelial cells in virus-induced demyelination, J. Immunol., 138: 3438.PubMedGoogle Scholar
  27. Roos, R. P., Firestone, S., Wollmann, R., Variakojis, D., and Arnason, B. G. W., 1982, The effect of short-term and chronic immunosuppression on Theiler’s virus demyelination, J. Neuroimmunol., 2: 223.PubMedCrossRefGoogle Scholar
  28. Roos, R. P., and Wollmann, R., 1984, DA strain of Theiler’s murine encephalomyelitis virus induces demyelination in nude mice, Ann. Neurol. 15: 494.PubMedCrossRefGoogle Scholar
  29. Rosenthal, A., Fujinami, R. S., and Lampert, P. W., 1986, Mechanism of Theiler’s virus-induced demyelination in nude mice, Lab. Invest., 54: 515.PubMedGoogle Scholar
  30. Theiler, M., 1934. Spontaneous encephalomyelitis of mice - a new virus disease, Science, 80: 122.PubMedCrossRefGoogle Scholar
  31. Wisniewski, H. M., and Bloom, B. R., 1975, Primary demyelination as a nonspecific consequence of a cell-mediated reaction, J. Exp. Med. 141: 346.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1987

Authors and Affiliations

  • Moses Rodriguez
    • 1
    • 2
  • Chella S. David
    • 2
  • Larry R. Pease
    • 2
  1. 1.Department of NeurologyMayo Clinic and Mayo FoundationRochesterUSA
  2. 2.Department of ImmunologyMayo Clinic and Mayo FoundationRochesterUSA

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