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. 1981;53(2):129–136. doi: 10.1007/BF00689993

Demyelination in mice resulting from infection with a mutant of Semliki Forest virus

B J Sheahan 1,, P N Barrett 2, G J Atkins 2
PMCID: PMC7086517  PMID: 6259872

Summary

Twelve of 34 weanling mice (35%) developed lesions in the brain and spinal cord following i.p. infection with 102 p.f.u. of a mutant of Semliki Forest virus (SFV). Six of 12 mice examined 13 days post infection (p.i.) showed meningo-encephalomyelitis with focal spongiform lesions in the grey and white matter. The spongiform lesions were characterised by necrosis of putative oligodendrocytes, myelinic vacuolation and mononuclear cell infiltration. Only one of six mice examined 21 days p.i. and one of six mice examined 28 days p.i. showed lesions which comprised reactive and dystrophic changes in the white matter. Spongiform lesions and pycnotic nuclei were not seen at these times. Viral nucleocapsids were seen in the early stages of the disease in putative necrotic oligodendrocytes. Mature virus particles were not seen. This was in contrast to mice infected with virulent wild-type SFV when lesions were more severe and were accompanied by large numbers of immature and mature virus particles. It is suggested that the demyelination in mice infected with mutant SFV results primarily from selective destruction of oligodendrocytes by the mutant virus.

Key words: Semliki Forest virus, Demyelinating diseases, Spongy degeneration, Oligodendrocytes

Footnotes

The study was supported by the Medical Research Council of Ireland

References

  1. 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]
  2. Blakemore WF. Observations on oligodendrocyte degeneration, the resolution of status spongiosus, and remyelination in cuprizone intoxication in mice. J Neurocytol. 1972;1:413–426. doi: 10.1007/BF01102943. [DOI] [PubMed] [Google Scholar]
  3. Bradish CJ, Allner K, Maber HB. The virulence of original and derived strains of Semliki Forest virus for mice, guinea pigs, and rabbits. J Gen Virol. 1971;12:141–160. doi: 10.1099/0022-1317-12-2-141. [DOI] [PubMed] [Google Scholar]
  4. Bradish CJ, Allner K. The early responses of mice to respiratory and intraperitoneal infection by defined virulent and avirulent strains of Semliki Forest virus. J Gen Virol. 1972;15:205–218. doi: 10.1099/0022-1317-15-3-205. [DOI] [PubMed] [Google Scholar]
  5. Bradish CJ, Allner K, Maber HB. Infection, interaction, and the expression of virulence by defined strains of Semliki Forest virus. J Gen Virol. 1972;16:359–372. doi: 10.1099/0022-1317-16-3-359. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Chew-Lim M, Webb HE, Jagelman S. The effect of irradiation on demyelination induced by avirulent Semliki Forest virus. Br J Exp Pathol. 1977;58:459–464. [PMC free article] [PubMed] [Google Scholar]
  8. Chew-Lim M, Scott T, Webb HE. An ultrastructure study of cerebellar lesions induced in mice by three inoculations of avirulent Semliki Forest virus. Acta Neuropathol (Berl) 1978;41:55–59. doi: 10.1007/BF00689557. [DOI] [PubMed] [Google Scholar]
  9. Chew-Lim M. Brain viral persistence and myelin damage in nude mice. Can J Comp Med. 1979;43:39–43. [PMC free article] [PubMed] [Google Scholar]
  10. Dal Canto MC, Lipton HC. Animal model of human disease. Multiple sclerosis. Animal model. Theiler's virus infection in mice. Am J Pathol. 1977;88:497–500. [PMC free article] [PubMed] [Google Scholar]
  11. Grimley PM, Friedman RM. Development of Semliki Forest virus in mouse brain. An electron-microscopic study. Exp Mol Pathol. 1970;12:1–13. doi: 10.1016/0014-4800(70)90070-5. [DOI] [PubMed] [Google Scholar]
  12. Herndon RM, Griffin DE, McCormick U, Weiner LP. Mouse hepatitis virus. Induced recurrent demyelination. Arch Neurol. 1975;32:32–35. doi: 10.1001/archneur.1975.00490430054008. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. 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]
  15. Lampert PW. Electron-microscopic studies on ordinary and hyperacute experimental allergic encephalomyelitis. Acta Neuropathol (Berl) 1967;9:99–126. doi: 10.1007/BF00691436. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Mackenzie A, Suckling AJ, Jagelman S, Wilson AM. Histopathological and enzyme histochemical changes in experimental Semliki Forest virus infection in mice and their relevance to scrapie. J Comp Pathol. 1978;88:335–343. doi: 10.1016/0021-9975(78)90038-5. [DOI] [PubMed] [Google Scholar]
  18. Nagashima K, Wege H, Meyermann R, ter Meulen V. Corona virus-induced subacute demyelinating encephalomyelitis in rats: a morphological analysis. Acta Neuropathol (Berl) 1978;44:63–70. doi: 10.1007/BF00691641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Pathak S, Webb HE. Possible mechanisms for the transport of Semliki Forest virus into and within mouse brain. An electronmicroscopic study. J Neurol Sci. 1974;23:175–184. doi: 10.1016/0022-510x(74)90221-4. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Penney JB, Wolinsky JS. Neuronal and oligodendroglial infection by the WW strain of Theiler's virus. Lab Invest. 1979;40:324–330. [PubMed] [Google Scholar]
  22. Seamer J, Randles WJ, Fitzgeorge R. The course of Semliki Forest virus infection in mice. Br J Exp Pathol. 1967;48:395–402. [PMC free article] [PubMed] [Google Scholar]
  23. Smithburn KC, Haddow AJ. Semliki Forest virus. I. Isolation and pathogenic properties. J Immunol. 1944;49:141–148. [Google Scholar]
  24. 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]
  25. 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]

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