Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1993 Jan;67(1):589–592. doi: 10.1128/jvi.67.1.589-592.1993

Theiler's virus infection of beta 2-microglobulin-deficient mice.

L Fiette 1, C Aubert 1, M Brahic 1, C P Rossi 1
PMCID: PMC237400  PMID: 8416386

Abstract

Theiler's virus, a murine picornavirus, persists in the central nervous systems of susceptible mice and induces a chronic demyelinating disease. Susceptibility or resistance to this disease is controlled in part by the H2-D locus of the major histocompatibility complex (MHC). For this reason, it has been proposed that CD8+ class I-restricted cytotoxic T cells play a main role in the pathogenesis of this viral infection. We recently reported the existence of anti-virus CD8+ cytotoxic T cells in the course of Theiler's virus infection. In the present study, we examined the role of these effector cells in mice in which the beta 2-microglobulin gene had been disrupted. These mice fail to express class I MHC molecules and therefore lack CD8+ T cells. The mice are derived from a C57BL/6 x 129/Ola cross and are H-2b, a haplotype associated with resistance to Theiler's virus infection. beta 2-Microglobulin-deficient mice (beta 2m-/-mice) failed to clear the virus, developed demyelination, and, interestingly, did not succumb to early infection. These results demonstrate that CD8+ T cells are required to clear Theiler's virus infection. In contrast with a current hypothesis, they also demonstrate that CD8+ T cells are not major mediators of the demyelinating disease.

Full text

PDF
589

Images in this article

590Image
on p.590

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aubert C., Chamorro M., Brahic M. Identification of Theiler's virus infected cells in the central nervous system of the mouse during demyelinating disease. Microb Pathog. 1987 Nov;3(5):319–326. doi: 10.1016/0882-4010(87)90002-7. [DOI] [PubMed] [Google Scholar]
  2. Brahic M., Bureau J. F., McAllister A. Genetic determinants of the demyelinating disease caused by Theiler's virus. Microb Pathog. 1991 Aug;11(2):77–84. doi: 10.1016/0882-4010(91)90001-q. [DOI] [PubMed] [Google Scholar]
  3. Brahic M., Haase A. T., Cash E. Simultaneous in situ detection of viral RNA and antigens. Proc Natl Acad Sci U S A. 1984 Sep;81(17):5445–5448. doi: 10.1073/pnas.81.17.5445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brahic M., Stroop W. G., Baringer J. R. Theiler's virus persists in glial cells during demyelinating disease. Cell. 1981 Oct;26(1 Pt 1):123–128. doi: 10.1016/0092-8674(81)90040-4. [DOI] [PubMed] [Google Scholar]
  5. Bureau J. F., Montagutelli X., Lefebvre S., Guénet J. L., Pla M., Brahic M. The interaction of two groups of murine genes determines the persistence of Theiler's virus in the central nervous system. J Virol. 1992 Aug;66(8):4698–4704. doi: 10.1128/jvi.66.8.4698-4704.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cash E., Bandeira A., Chirinian S., Brahic M. Characterization of B lymphocytes present in the demyelinating lesions induced by Theiler's virus. J Immunol. 1989 Aug 1;143(3):984–988. [PubMed] [Google Scholar]
  7. Chamorro M., Aubert C., Brahic M. Demyelinating lesions due to Theiler's virus are associated with ongoing central nervous system infection. J Virol. 1986 Mar;57(3):992–997. doi: 10.1128/jvi.57.3.992-997.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Eichelberger M., Allan W., Zijlstra M., Jaenisch R., Doherty P. C. Clearance of influenza virus respiratory infection in mice lacking class I major histocompatibility complex-restricted CD8+ T cells. J Exp Med. 1991 Oct 1;174(4):875–880. doi: 10.1084/jem.174.4.875. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fujinami R. S., Rosenthal A., Lampert P. W., Zurbriggen A., Yamada M. Survival of athymic (nu/nu) mice after Theiler's murine encephalomyelitis virus infection by passive administration of neutralizing monoclonal antibody. J Virol. 1989 May;63(5):2081–2087. doi: 10.1128/jvi.63.5.2081-2087.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Habu S., Fukui H., Shimamura K., Kasai M., Nagai Y., Okumura K., Tamaoki N. In vivo effects of anti-asialo GM1. I. Reduction of NK activity and enhancement of transplanted tumor growth in nude mice. J Immunol. 1981 Jul;127(1):34–38. [PubMed] [Google Scholar]
  11. Herberman R. B., Holden H. T. Natural cell-mediated immunity. Adv Cancer Res. 1978;27:305–377. doi: 10.1016/s0065-230x(08)60936-7. [DOI] [PubMed] [Google Scholar]
  12. Koller B. H., Marrack P., Kappler J. W., Smithies O. Normal development of mice deficient in beta 2M, MHC class I proteins, and CD8+ T cells. Science. 1990 Jun 8;248(4960):1227–1230. doi: 10.1126/science.2112266. [DOI] [PubMed] [Google Scholar]
  13. Liao N. S., Bix M., Zijlstra M., Jaenisch R., Raulet D. MHC class I deficiency: susceptibility to natural killer (NK) cells and impaired NK activity. Science. 1991 Jul 12;253(5016):199–202. doi: 10.1126/science.1853205. [DOI] [PubMed] [Google Scholar]
  14. Lindsley M. D., Thiemann R., Rodriguez M. Cytotoxic T cells isolated from the central nervous systems of mice infected with Theiler's virus. J Virol. 1991 Dec;65(12):6612–6620. doi: 10.1128/jvi.65.12.6612-6620.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lipton H. L., Canto C. D. Contrasting effects of immunosuppression on Theiler's virus infection in mice. Infect Immun. 1977 Mar;15(3):903–909. doi: 10.1128/iai.15.3.903-909.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lipton H. L., Dal Canto M. C. Susceptibility of inbred mice to chronic central nervous system infection by Theiler's murine encephalomyelitis virus. Infect Immun. 1979 Oct;26(1):369–374. doi: 10.1128/iai.26.1.369-374.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lipton H. L. Theiler's virus infection in mice: an unusual biphasic disease process leading to demyelination. Infect Immun. 1975 May;11(5):1147–1155. doi: 10.1128/iai.11.5.1147-1155.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Momburg F., Koch N., Möller P., Moldenhauer G., Hämmerling G. J. In vivo induction of H-2K/D antigens by recombinant interferon-gamma. Eur J Immunol. 1986 May;16(5):551–557. doi: 10.1002/eji.1830160516. [DOI] [PubMed] [Google Scholar]
  19. Muller D., Koller B. H., Whitton J. L., LaPan K. E., Brigman K. K., Frelinger J. A. LCMV-specific, class II-restricted cytotoxic T cells in beta 2-microglobulin-deficient mice. Science. 1992 Mar 20;255(5051):1576–1578. doi: 10.1126/science.1347959. [DOI] [PubMed] [Google Scholar]
  20. Pena Rossi C., McAllister A., Fiette L., Brahic M. Theiler's virus infection induces a specific cytotoxic T lymphocyte response. Cell Immunol. 1991 Dec;138(2):341–348. doi: 10.1016/0008-8749(91)90158-8. [DOI] [PubMed] [Google Scholar]
  21. Rodriguez M., David C. S. Demyelination induced by Theiler's virus: influence of the H-2 haplotype. J Immunol. 1985 Sep;135(3):2145–2148. [PubMed] [Google Scholar]
  22. Rodriguez M., Lafuse W. P., Leibowitz J., David C. S. Partial suppression of Theiler's virus-induced demyelination in vivo by administration of monoclonal antibodies to immune-response gene products (Ia antigens). Neurology. 1986 Jul;36(7):964–970. doi: 10.1212/wnl.36.7.964. [DOI] [PubMed] [Google Scholar]
  23. Rodriguez M., Sriram S. Successful therapy of Theiler's virus-induced demyelination (DA strain) with monoclonal anti-Lyt-2 antibody. J Immunol. 1988 May 1;140(9):2950–2955. [PubMed] [Google Scholar]
  24. Rossi C. P., Cash E., Aubert C., Coutinho A. Role of the humoral immune response in resistance to Theiler's virus infection. J Virol. 1991 Jul;65(7):3895–3899. doi: 10.1128/jvi.65.7.3895-3899.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Welsh C. J., Tonks P., Nash A. A., Blakemore W. F. The effect of L3T4 T cell depletion on the pathogenesis of Theiler's murine encephalomyelitis virus infection in CBA mice. J Gen Virol. 1987 Jun;68(Pt 6):1659–1667. doi: 10.1099/0022-1317-68-6-1659. [DOI] [PubMed] [Google Scholar]
  26. Zijlstra M., Bix M., Simister N. E., Loring J. M., Raulet D. H., Jaenisch R. Beta 2-microglobulin deficient mice lack CD4-8+ cytolytic T cells. Nature. 1990 Apr 19;344(6268):742–746. doi: 10.1038/344742a0. [DOI] [PubMed] [Google Scholar]
  27. Zurbriggen A., Fujinami R. S. Theiler's virus infection in nude mice: viral RNA in vascular endothelial cells. J Virol. 1988 Oct;62(10):3589–3596. doi: 10.1128/jvi.62.10.3589-3596.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES