Skip to main content
Springer Nature - PMC COVID-19 Collection logoLink to Springer Nature - PMC COVID-19 Collection
. 1983;60(3):257–265. doi: 10.1007/BF00691874

Oligodendrocyte infection and demyelination produced in mice by the M9 mutant of Semliki Forest virus

B J Sheahan 1, M C Gates 2, J F Caffrey 1, G J Atkins 2
PMCID: PMC7086535  PMID: 6310927

Summary

Intraperitoneal inoculation with the M9 mutant of Semliki Forest virus caused focal demyelinating encephalomyelitis in weanling BALB/c and C57BL/6 mice. Demyelination was more severe in BALB/c than in C57BL/6 mice. Virus particles were seen in oligodendrocytes in areas of myelin vacuolation 5 and 7 days post inoculation (DPI). Oligodendrocytes containing virus in BALB/c mice showed hypertrophy and vacuolar degeneration. There was a mononuclear cell infiltrate and lymphocytes and necrotic cells were present in vacuoles in myelin sheaths. Demyelinating plaques containing macrophages laden with myelin debris were most prominent 14 DPI when virus was cleared from the brain. Remyelination of the central type occurred 28 DPI in BALB/c mice. These findings indicate that direct virus-induced injury to oligodendrocytes has a major role in the initiation of inflammation and demyelination in this model system.

Key words: Semliki Forest virus, Oligodendrocytes, Demyelination, Remyelination

Footnotes

Supported by the Medical Research Council of Ireland

References

  1. Arnason BGW, Winkler GF, Hadler NM. Cell-mediated demyelination of peripheral nerve in tissue culture. Lab Invest. 1969;21:1–10. [PubMed] [Google Scholar]
  2. Atkins GJ, Sheahan BJ. Semliki Forest virus neurovirulence mutants have altered cytopathogenicity for cells of the central nervous system. Infect Immun. 1982;36:333–341. doi: 10.1128/iai.36.1.333-341.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barrett PN, Sheahan BJ, Atkins GJ. Isolation and preliminary characterization of Semliki Forest virus mutants with altered virulence. J Gen Virol. 1980;49:141–147. doi: 10.1099/0022-1317-49-1-141. [DOI] [PubMed] [Google Scholar]
  4. Berger ML. Humoral and cell-mediated immune mechanisms in the production of pathology in avirulent Semliki Forest virus encephalitis. Infect Immun. 1980;30:244–253. doi: 10.1128/iai.30.1.244-253.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Blakemore WF. Remyelination in the CNS. In: Acosta Vidrio E, Fedoroff S, editors. Glial and neuronal cell biology. New York: Liss; 1981. pp. 105–109. [Google Scholar]
  6. Cammer W, Bloom BR, Norton WT, Gordon S. Degradation of basic protein in myelin by neutral proteases secreted by stimulated macrophages — a possible mechanism of inflammatory demyelination. Proc Natl Acad Sci USA. 1978;75:1554–1558. doi: 10.1073/pnas.75.3.1554. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chew-Lim M. Mouse encephalitis induced by avirulent Semliki Forest virus. Vet Pathol. 1975;12:387–393. doi: 10.1177/0300985875012005-00605. [DOI] [PubMed] [Google Scholar]
  8. Chew-Lim M, Suckling AJ, Webb HE. Demyelination in mice after two or three infections with avirulent Semliki Forest virus. Vet Pathol. 1977;14:67–72. doi: 10.1177/030098587701400108. [DOI] [PubMed] [Google Scholar]
  9. Dal Canto MC, Rabinowitz SG. Experimental models of virus-induced demyelination of the central nervous system. Ann Neurol. 1982;11:109–127. doi: 10.1002/ana.410110202. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fleury HJA, Sheppard RD, Bornstein MB, Raine CS. Further ultrastructural observations of virus morphogenesis and myelin pathology in JHM virus encephalomyelitis. Neuropathol Appl Neurobiol. 1980;6:165–179. doi: 10.1111/j.1365-2990.1980.tb00288.x. [DOI] [PubMed] [Google Scholar]
  11. Herndon RM, Price DL, Weiner LP. Regeneration of oligodendroglia during recovery from demyelinating disease. Science. 1977;195:693–694. doi: 10.1126/science.190678. [DOI] [PubMed] [Google Scholar]
  12. Jagelman S, Suckling AJ, Webb HE, Bowen ETW. The pathogenesis of avirulent Semliki Forest virus infections in athymic nude mice. J Gen Virol. 1978;41:599–607. doi: 10.1099/0022-1317-41-3-599. [DOI] [PubMed] [Google Scholar]
  13. Kelly WR, Blakemore WF, Jagelman S, Webb HE. Demyelination induced in mice by avirulent Semliki Forest virus. II. An ultrastructural study of focal demyelination in the brain. Neuropathol Appl Neurobiol. 1982;8:43–53. doi: 10.1111/j.1365-2990.1982.tb00256.x. [DOI] [PubMed] [Google Scholar]
  14. Lampert PW, Sims JK, Kniazeff AJ. Mechanism of demyelination in JHM virus encephalomyelitis. Electronmicroscopic studies. Acta Neuropathol (Berl) 1973;24:76–85. doi: 10.1007/BF00691421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Langford LA, Coggeshall RE. The use of potassium ferricyanide in neural fixation. Anat Rec. 1980;197:297–303. doi: 10.1002/ar.1091970304. [DOI] [PubMed] [Google Scholar]
  16. Pathak S, Webb HE, Oaten SW, Bateman S. An electronmicroscopic study of the development of virulent and avirulent strains of Semliki Forest virus in mouse brain. J Neurol Sci. 1976;28:289–300. doi: 10.1016/0022-510x(76)90022-8. [DOI] [PubMed] [Google Scholar]
  17. Pathak S, Webb HE. An electron-microscopic study of avirulent and virulent Semliki Forest virus in the brains of different ages of mice. J Neurol Sci. 1978;39:199–211. doi: 10.1016/0022-510x(78)90123-5. [DOI] [PubMed] [Google Scholar]
  18. Powell HC, Lampert PW. Oligodendrocytes and their myelinplasma membrane connections in JHM mouse hepatitis virus encephalomyelitis. Lab Invest. 1975;33:440–445. [PubMed] [Google Scholar]
  19. Sheahan BJ, Barrett PN, Atkins GJ. Demyelination in mice resulting from infection with a mutant of Semliki Forest virus. Acta Neuropathol (Berl) 1981;53:129–136. doi: 10.1007/BF00689993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Stohlman SA, Weiner LP. Chronic central nervous system demyelination in mice after JHM virus infection. Neurology. 1981;31:38–44. doi: 10.1212/wnl.31.1.38. [DOI] [PubMed] [Google Scholar]
  21. Suckling AJ, Pathak S, Jagelman S, Webb HE. Virus-associated demyelination. A model using avirulent Semliki Forest virus infection of mice. J Neurol Sci. 1978;39:147–154. doi: 10.1016/0022-510x(78)90195-8. [DOI] [PubMed] [Google Scholar]
  22. Suckling AJ, Jagelman S, Illavia SJ, Webb HE. The effect of mouse strain on the pathogenesis of the encephalitis and demyelination induced by avirulent Semliki Forest virus infections. Br J Exp Pathol. 1980;61:281–284. [PMC free article] [PubMed] [Google Scholar]
  23. Wege H, Siddell S, ter Meulen V. The biology and pathogenesis of coronaviruses. Curr Top Microbiol Immunol. 1982;99:165–200. doi: 10.1007/978-3-642-68528-6_5. [DOI] [PubMed] [Google Scholar]
  24. Weiner LP. Pathogenesis of demyelination induced by a mouse hepatitis virus (JHM virus) Arch Neurol. 1973;28:298–303. doi: 10.1001/archneur.1973.00490230034003. [DOI] [PubMed] [Google Scholar]
  25. Weiner LP, Johnson RT, Herndon RM. Viral infections and demyelinating diseases. New Engl J Med. 1973;288:1103–1110. doi: 10.1056/NEJM197305242882106. [DOI] [PubMed] [Google Scholar]
  26. Wisniewski HM. Immunopathology of demyelination in autoimmune diseases and virus infections. Br Med Bull. 1977;33:54–59. doi: 10.1093/oxfordjournals.bmb.a071397. [DOI] [PubMed] [Google Scholar]

Articles from Acta Neuropathologica are provided here courtesy of Nature Publishing Group

RESOURCES