Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1995 Sep;69(9):5599–5606. doi: 10.1128/jvi.69.9.5599-5606.1995

The neurovirulent GDVII strain of Theiler's virus can replicate in glial cells.

J P Simas 1, H Dyson 1, J K Fazakerley 1
PMCID: PMC189416  PMID: 7637006

Abstract

The distribution, spread, neuropathology, tropism, and persistence of the neurovirulent GDVII strain of Theiler's virus in the central nervous system (CNS) was investigated in mice susceptible and resistant to chronic demyelinating infection with TO strains. Following intracerebral inoculation, the virus spread rapidly to specific areas of the CNS. There were, however, specific structures in which infection was consistently undetectable. Virus spread both between adjacent cell bodies and along neuronal pathways. The distribution of the infection was dependent on the site of inoculation. The majority of viral RNA-positive cells were neurons. Many astrocytes were also positive. Infection of both of these cell types was lytic. In contrast, viral RNA-positive oligodendrocytes were rare and were observed only in well-established areas of infection. The majority of oligodendrocytes in these areas were viral RNA negative and were often the major cell type remaining; however, occasional destruction of these cells was observed. No differences in any of the above parameters were observed between CBA and BALB/c mice, susceptible and resistant, respectively, to chronic CNS demyelinating infection with TO strains of Theiler's virus. By using Southern blot hybridization to detect reverse-transcribed PCR-amplified viral RNA sequences, no virus persistence could be detected in the CNS of immunized mice surviving infection with GDVII. In conclusion, the GDVII strain of Theiler's murine encephalomyelitis virus cannot persist in the CNS, but this is not consequent upon an inability to infect glial cells, including oligodendrocytes.

Full Text

The Full Text of this article is available as a PDF (1.3 MB).

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. Azoulay A., Brahic M., Bureau J. F. FVB mice transgenic for the H-2Db gene become resistant to persistent infection by Theiler's virus. J Virol. 1994 Jun;68(6):4049–4052. doi: 10.1128/jvi.68.6.4049-4052.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Blakemore W. F., Welsh C. J., Tonks P., Nash A. A. Observations on demyelinating lesions induced by Theiler's virus in CBA mice. Acta Neuropathol. 1988;76(6):581–589. doi: 10.1007/BF00689596. [DOI] [PubMed] [Google Scholar]
  4. Borrow P., Tonks P., Welsh C. J., Nash A. A. The role of CD8+T cells in the acute and chronic phases of Theiler's murine encephalomyelitis virus-induced disease in mice. J Gen Virol. 1992 Jul;73(Pt 7):1861–1865. doi: 10.1099/0022-1317-73-7-1861. [DOI] [PubMed] [Google Scholar]
  5. Cash E., Chamorro M., Brahic M. Minus-strand RNA synthesis in the spinal cords of mice persistently infected with Theiler's virus. J Virol. 1988 May;62(5):1824–1826. doi: 10.1128/jvi.62.5.1824-1826.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cash E., Chamorro M., Brahic M. Quantitation, with a new assay, of Theiler's virus capsid protein in the central nervous system of mice. J Virol. 1986 Nov;60(2):558–563. doi: 10.1128/jvi.60.2.558-563.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cash E., Chamorro M., Brahic M. Theiler's virus RNA and protein synthesis in the central nervous system of demyelinating mice. Virology. 1985 Jul 15;144(1):290–294. doi: 10.1016/0042-6822(85)90327-7. [DOI] [PubMed] [Google Scholar]
  8. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  9. Dal Canto M. C., Lipton H. L. Primary demyelination in Theiler's virus infection. An ultrastructural study. Lab Invest. 1975 Dec;33(6):626–637. [PubMed] [Google Scholar]
  10. Dal Canto M. C., Lipton H. L. Ultrastructural immunohistochemical localization of virus in acute and chronic demyelinating Theiler's virus infection. Am J Pathol. 1982 Jan;106(1):20–29. [PMC free article] [PubMed] [Google Scholar]
  11. Dutko F. J., Oldstone M. B. Cytomegalovirus causes a latent infection in undifferentiated cells and is activated by induction of cell differentiation. J Exp Med. 1981 Nov 1;154(5):1636–1651. doi: 10.1084/jem.154.5.1636. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Embretson J., Zupancic M., Ribas J. L., Burke A., Racz P., Tenner-Racz K., Haase A. T. Massive covert infection of helper T lymphocytes and macrophages by HIV during the incubation period of AIDS. Nature. 1993 Mar 25;362(6418):359–362. doi: 10.1038/362359a0. [DOI] [PubMed] [Google Scholar]
  13. Fan S. T., Hsia K., Edgington T. S. Upregulation of human immunodeficiency virus-1 in chronically infected monocytic cell line by both contact with endothelial cells and cytokines. Blood. 1994 Sep 1;84(5):1567–1572. [PubMed] [Google Scholar]
  14. Fazakerley J. K., Pathak S., Scallan M., Amor S., Dyson H. Replication of the A7(74) strain of Semliki Forest virus is restricted in neurons. Virology. 1993 Aug;195(2):627–637. doi: 10.1006/viro.1993.1414. [DOI] [PubMed] [Google Scholar]
  15. Fiette L., Aubert C., Brahic M., Rossi C. P. Theiler's virus infection of beta 2-microglobulin-deficient mice. J Virol. 1993 Jan;67(1):589–592. doi: 10.1128/jvi.67.1.589-592.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Frankel G., Friedmann A., Amir A., David Y., Shahar A. Theiler's virus replication in isolated Schwann cell cultures. J Neurosci Res. 1986;15(2):127–136. doi: 10.1002/jnr.490150202. [DOI] [PubMed] [Google Scholar]
  17. Fu J. L., Stein S., Rosenstein L., Bodwell T., Routbort M., Semler B. L., Roos R. P. Neurovirulence determinants of genetically engineered Theiler viruses. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4125–4129. doi: 10.1073/pnas.87.11.4125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Fu J., Rodriguez M., Roos R. P. Strains from both Theiler's virus subgroups encode a determinant for demyelination. J Virol. 1990 Dec;64(12):6345–6348. doi: 10.1128/jvi.64.12.6345-6348.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Gönczöl E., Andrews P. W., Plotkin S. A. Cytomegalovirus replicates in differentiated but not in undifferentiated human embryonal carcinoma cells. Science. 1984 Apr 13;224(4645):159–161. doi: 10.1126/science.6322309. [DOI] [PubMed] [Google Scholar]
  20. Jarousse N., Grant R. A., Hogle J. M., Zhang L., Senkowski A., Roos R. P., Michiels T., Brahic M., McAllister A. A single amino acid change determines persistence of a chimeric Theiler's virus. J Virol. 1994 May;68(5):3364–3368. doi: 10.1128/jvi.68.5.3364-3368.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lehrich J. R., Arnason B. G., Hochberg F. H. Demyelinative myelopathy in mice induced by the DA virus. J Neurol Sci. 1976 Oct;29(2-4):149–160. doi: 10.1016/0022-510x(76)90167-2. [DOI] [PubMed] [Google Scholar]
  22. Lindsley M. D., Rodriguez M. Characterization of the inflammatory response in the central nervous system of mice susceptible or resistant to demyelination by Theiler's virus. J Immunol. 1989 Apr 15;142(8):2677–2682. [PubMed] [Google Scholar]
  23. 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]
  24. Lipton H. L., Calenoff M., Bandyopadhyay P., Miller S. D., Dal Canto M. C., Gerety S., Jensen K. The 5' noncoding sequences from a less virulent Theiler's virus dramatically attenuate GDVII neurovirulence. J Virol. 1991 Aug;65(8):4370–4377. doi: 10.1128/jvi.65.8.4370-4377.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Lipton H. L. Persistent Theiler's murine encephalomyelitis virus infection in mice depends on plaque size. J Gen Virol. 1980 Jan;46(1):169–177. doi: 10.1099/0022-1317-46-1-169. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Liu C., Collins J., Sharp E. The pathogenesis of Theiler's GD VII encephalomyelitis virus infection in mice as studied by immunofluorescent technique and infectivity titrations. J Immunol. 1967 Jan;98(1):46–55. [PubMed] [Google Scholar]
  28. Ohara Y., Konno H., Iwasaki Y., Yamamoto T., Terunuma H., Suzuki H. Cytotropism of Theiler's murine encephalomyelitis viruses in oligodendrocyte-enriched cultures. Arch Virol. 1990;114(3-4):293–298. doi: 10.1007/BF01310760. [DOI] [PubMed] [Google Scholar]
  29. Ohara Y., Stein S., Fu J. L., Stillman L., Klaman L., Roos R. P. Molecular cloning and sequence determination of DA strain of Theiler's murine encephalomyelitis viruses. Virology. 1988 May;164(1):245–255. doi: 10.1016/0042-6822(88)90642-3. [DOI] [PubMed] [Google Scholar]
  30. Ozden S., Tangy F., Chamorro M., Brahic M. Theiler's virus genome is closely related to that of encephalomyocarditis virus, the prototype cardiovirus. J Virol. 1986 Dec;60(3):1163–1165. doi: 10.1128/jvi.60.3.1163-1165.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Pasick J. M., Dales S. Infection by coronavirus JHM of rat neurons and oligodendrocyte-type-2 astrocyte lineage cells during distinct developmental stages. J Virol. 1991 Sep;65(9):5013–5028. doi: 10.1128/jvi.65.9.5013-5028.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. 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]
  33. Pevear D. C., Borkowski J., Calenoff M., Oh C. K., Ostrowski B., Lipton H. L. Insights into Theiler's virus neurovirulence based on a genomic comparison of the neurovirulent GDVII and less virulent BeAn strains. Virology. 1988 Jul;165(1):1–12. doi: 10.1016/0042-6822(88)90652-6. [DOI] [PubMed] [Google Scholar]
  34. Pevear D. C., Calenoff M., Rozhon E., Lipton H. L. Analysis of the complete nucleotide sequence of the picornavirus Theiler's murine encephalomyelitis virus indicates that it is closely related to cardioviruses. J Virol. 1987 May;61(5):1507–1516. doi: 10.1128/jvi.61.5.1507-1516.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Poli G., Kinter A. L., Fauci A. S. Interleukin 1 induces expression of the human immunodeficiency virus alone and in synergy with interleukin 6 in chronically infected U1 cells: inhibition of inductive effects by the interleukin 1 receptor antagonist. Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):108–112. doi: 10.1073/pnas.91.1.108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Raible D. W., McMorris F. A. Cyclic AMP regulates the rate of differentiation of oligodendrocytes without changing the lineage commitment of their progenitors. Dev Biol. 1989 Jun;133(2):437–446. doi: 10.1016/0012-1606(89)90047-x. [DOI] [PubMed] [Google Scholar]
  37. Rodriguez M., Dunkel A. J., Thiemann R. L., Leibowitz J., Zijlstra M., Jaenisch R. Abrogation of resistance to Theiler's virus-induced demyelination in H-2b mice deficient in beta 2-microglobulin. J Immunol. 1993 Jul 1;151(1):266–276. [PubMed] [Google Scholar]
  38. Rodriguez M., Leibowitz J. L., Lampert P. W. Persistent infection of oligodendrocytes in Theiler's virus-induced encephalomyelitis. Ann Neurol. 1983 Apr;13(4):426–433. doi: 10.1002/ana.410130409. [DOI] [PubMed] [Google Scholar]
  39. Rodriguez M., Roos R. P. Pathogenesis of early and late disease in mice infected with Theiler's virus, using intratypic recombinant GDVII/DA viruses. J Virol. 1992 Jan;66(1):217–225. doi: 10.1128/jvi.66.1.217-225.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Shahar A., Frankel G., David Y., Friedmann A. In vitro cytotoxicity and demyelination induced by Theiler viruses in cultures of spinal cord slices. J Neurosci Res. 1986;16(4):671–681. doi: 10.1002/jnr.490160408. [DOI] [PubMed] [Google Scholar]
  41. Stroop W. G., Baringer J. R., Brahic M. Detection of Theiler's virus RNA in mouse central nervous system by in situ hybridization. Lab Invest. 1981 Dec;45(6):504–509. [PubMed] [Google Scholar]
  42. Tangy F., McAllister A., Aubert C., Brahic M. Determinants of persistence and demyelination of the DA strain of Theiler's virus are found only in the VP1 gene. J Virol. 1991 Mar;65(3):1616–1618. doi: 10.1128/jvi.65.3.1616-1618.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Wada Y., Fujinami R. S. Viral infection and dissemination through the olfactory pathway and the limbic system by Theiler's virus. Am J Pathol. 1993 Jul;143(1):221–229. [PMC free article] [PubMed] [Google Scholar]
  44. Wada Y., Pierce M. L., Fujinami R. S. Importance of amino acid 101 within capsid protein VP1 for modulation of Theiler's virus-induced disease. J Virol. 1994 Feb;68(2):1219–1223. doi: 10.1128/jvi.68.2.1219-1223.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES