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. 1997 Jul;71(7):5025–5030. doi: 10.1128/jvi.71.7.5025-5030.1997

The shiverer mutation affects the persistence of Theiler's virus in the central nervous system.

F Bihl 1, C Pena-Rossi 1, J L Guénet 1, M Brahic 1, J F Bureau 1
PMCID: PMC191735  PMID: 9188567

Abstract

Theiler's virus persists in the white matter of the spinal cord of genetically susceptible mice and causes primary demyelination. The virus persists in macrophages/microglial cells, but also in oligodendrocytes, the myelin-forming cells. Susceptibility/resistance to this chronic infection has been mapped to several loci including one tentatively located in the telomeric region of chromosome 18, close to the myelin basic protein locus (Mbp locus). To determine if the MBP gene influences viral persistence, we inoculated C3H mice bearing the shiverer mutation, a 20-kb deletion in the gene. Whereas control C3H mice were of intermediate susceptibility, C3H mice heterozygous for the mutation were very susceptible, and those homozygous for the mutation were completely resistant. This resistance was not immune mediated. Furthermore, C3H/101H mice homozygous for a point mutation in the gene coding for the proteolipid protein of myelin, the rumpshaker mutation, were resistant. These results strongly support the view that oligodendrocytes are a necessary viral target for the establishment of a persistent infection by Theiler's virus.

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Selected References

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  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. Boison D., Büssow H., D'Urso D., Müller H. W., Stoffel W. Adhesive properties of proteolipid protein are responsible for the compaction of CNS myelin sheaths. J Neurosci. 1995 Aug;15(8):5502–5513. doi: 10.1523/JNEUROSCI.15-08-05502.1995. [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., Bihl F., Lefebvre S., Guénet J. L., Brahic M. Mapping loci influencing the persistence of Theiler's virus in the murine central nervous system. Nat Genet. 1993 Sep;5(1):87–91. doi: 10.1038/ng0993-87. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Campagnoni A. T., Pribyl T. M., Campagnoni C. W., Kampf K., Amur-Umarjee S., Landry C. F., Handley V. W., Newman S. L., Garbay B., Kitamura K. Structure and developmental regulation of Golli-mbp, a 105-kilobase gene that encompasses the myelin basic protein gene and is expressed in cells in the oligodendrocyte lineage in the brain. J Biol Chem. 1993 Mar 5;268(7):4930–4938. [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. Clatch R. J., Miller S. D., Metzner R., Dal Canto M. C., Lipton H. L. Monocytes/macrophages isolated from the mouse central nervous system contain infectious Theiler's murine encephalomyelitis virus (TMEV). Virology. 1990 May;176(1):244–254. doi: 10.1016/0042-6822(90)90249-q. [DOI] [PubMed] [Google Scholar]
  10. Dal Canto M. C., Lipton H. L. Recurrent demyelination in chronic central nervous system infection produced by Theiler's murine encephalomyelitis virus. J Neurol Sci. 1979 Aug;42(3):391–405. doi: 10.1016/0022-510x(79)90172-2. [DOI] [PubMed] [Google Scholar]
  11. Fritz R. B., Kalvakolanu I. Thymic expression of the golli-myelin basic protein gene in the SJL/J mouse. J Neuroimmunol. 1995 Mar;57(1-2):93–99. doi: 10.1016/0165-5728(94)00167-m. [DOI] [PubMed] [Google Scholar]
  12. Griffiths I. R., Scott I., McCulloch M. C., Barrie J. A., McPhilemy K., Cattanach B. M. Rumpshaker mouse: a new X-linked mutation affecting myelination: evidence for a defect in PLP expression. J Neurocytol. 1990 Apr;19(2):273–283. doi: 10.1007/BF01217305. [DOI] [PubMed] [Google Scholar]
  13. Kitamura K., Newman S. L., Campagnoni C. W., Verdi J. M., Mohandas T., Handley V. W., Campagnoni A. T. Expression of a novel transcript of the myelin basic protein gene. J Neurochem. 1990 Jun;54(6):2032–2041. doi: 10.1111/j.1471-4159.1990.tb04908.x. [DOI] [PubMed] [Google Scholar]
  14. Landry C. F., Ellison J. A., Pribyl T. M., Campagnoni C., Kampf K., Campagnoni A. T. Myelin basic protein gene expression in neurons: developmental and regional changes in protein targeting within neuronal nuclei, cell bodies, and processes. J Neurosci. 1996 Apr 15;16(8):2452–2462. doi: 10.1523/JNEUROSCI.16-08-02452.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lipton H. L., Dal Canto M. C. Chronic neurologic disease in Theiler's virus infection of SJL/J mice. J Neurol Sci. 1976 Nov;30(1):201–207. doi: 10.1016/0022-510x(76)90267-7. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Love J. M., Knight A. M., McAleer M. A., Todd J. A. Towards construction of a high resolution map of the mouse genome using PCR-analysed microsatellites. Nucleic Acids Res. 1990 Jul 25;18(14):4123–4130. doi: 10.1093/nar/18.14.4123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Macklin W. B., Campagnoni C. W., Deininger P. L., Gardinier M. V. Structure and expression of the mouse myelin proteolipid protein gene. J Neurosci Res. 1987;18(3):383–394. doi: 10.1002/jnr.490180302. [DOI] [PubMed] [Google Scholar]
  19. Melvold R. W., Jokinen D. M., Knobler R. L., Lipton H. L. Variations in genetic control of susceptibility to Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease. I. Differences between susceptible SJL/J and resistant BALB/c strains map near the T cell beta-chain constant gene on chromosome 6. J Immunol. 1987 Mar 1;138(5):1429–1433. [PubMed] [Google Scholar]
  20. Melvold R. W., Jokinen D. M., Miller S. D., Dal Canto M. C., Lipton H. L. Identification of a locus on mouse chromosome 3 involved in differential susceptibility to Theiler's murine encephalomyelitis virus-induced demyelinating disease. J Virol. 1990 Feb;64(2):686–690. doi: 10.1128/jvi.64.2.686-690.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Molineaux S. M., Engh H., de Ferra F., Hudson L., Lazzarini R. A. Recombination within the myelin basic protein gene created the dysmyelinating shiverer mouse mutation. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7542–7546. doi: 10.1073/pnas.83.19.7542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Montagutelli X., Serikawa T., Guénet J. L. PCR-analyzed microsatellites: data concerning laboratory and wild-derived mouse inbred strains. Mamm Genome. 1991;1(4):255–259. doi: 10.1007/BF00352333. [DOI] [PubMed] [Google Scholar]
  23. Nagara H., Suzuki K., Tateishi J. Radial component of central myelin in shiverer mouse. Brain Res. 1983 Mar 21;263(2):336–339. doi: 10.1016/0006-8993(83)90325-6. [DOI] [PubMed] [Google Scholar]
  24. Privat A., Jacque C., Bourre J. M., Dupouey P., Baumann N. Absence of the major dense line in myelin of the mutant mouse "shiverer". Neurosci Lett. 1979 Apr;12(1):107–112. doi: 10.1016/0304-3940(79)91489-7. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Rosenbluth J. Central myelin in the mouse mutant shiverer. J Comp Neurol. 1980 Dec 1;194(3):639–648. doi: 10.1002/cne.901940310. [DOI] [PubMed] [Google Scholar]
  27. Rossi C. P., Delcroix M., Huitinga I., McAllister A., van Rooijen N., Claassen E., Brahic M. Role of macrophages during Theiler's virus infection. J Virol. 1997 Apr;71(4):3336–3340. doi: 10.1128/jvi.71.4.3336-3340.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Schneider A., Montague P., Griffiths I., Fanarraga M., Kennedy P., Brophy P., Nave K. A. Uncoupling of hypomyelination and glial cell death by a mutation in the proteolipid protein gene. Nature. 1992 Aug 27;358(6389):758–761. doi: 10.1038/358758a0. [DOI] [PubMed] [Google Scholar]
  29. Tienari P. J., Wikström J., Sajantila A., Palo J., Peltonen L. Genetic susceptibility to multiple sclerosis linked to myelin basic protein gene. Lancet. 1992 Oct 24;340(8826):987–991. doi: 10.1016/0140-6736(92)93007-a. [DOI] [PubMed] [Google Scholar]
  30. Zelenika D., Grima B., Pessac B. A new family of transcripts of the myelin basic protein gene: expression in brain and in immune system. J Neurochem. 1993 Apr;60(4):1574–1577. doi: 10.1111/j.1471-4159.1993.tb03325.x. [DOI] [PubMed] [Google Scholar]

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