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Demyelination in mice resulting from infection with a mutant of Semliki Forest virus
Abstract:
Twelve of 34 weanling mice (35%) developed lesions in the brain and spinal cord following i.p. infection with 10(2) 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.
Insights
A Semliki Forest virus (SFV) mutant caused brain and spinal cord lesions in mice, characterized by oligodendrocyte destruction and demyelination. This suggests selective viral targeting of these cells leads to disease.
Area of Science:
- Neurovirology
- Immunology
- Pathology
Background:
- Semliki Forest virus (SFV) is a neurotropic alphavirus.
- Viral infections can cause central nervous system (CNS) damage and demyelination.
- Understanding viral pathogenesis is crucial for developing treatments.
Purpose of the Study:
- To investigate the neuropathogenesis of a mutant SFV strain in weanling mice.
- To characterize the lesions and viral presence in the CNS following infection.
- To elucidate the mechanism of demyelination induced by the mutant SFV.
Main Methods:
- Intraperitoneal (i.p.) infection of weanling mice with a mutant SFV strain.
- Histopathological examination of brain and spinal cord tissues at various time points post-infection (p.i.).
- Electron microscopy to identify viral nucleocapsids and particles within affected cells.
Main Results:
- 35% of infected mice developed CNS lesions.
- Early lesions (13 days p.i.) showed meningo-encephalomyelitis with spongiform changes, oligodendrocyte necrosis, and myelin vacuolation.
- Later stages (21 and 28 days p.i.) exhibited reactive and dystrophic white matter changes, without spongiform lesions.
- Viral nucleocapsids were observed in necrotic oligodendrocytes, but mature virus particles were absent.
Conclusions:
- The mutant SFV strain induces demyelination primarily through selective destruction of oligodendrocytes.
- The absence of mature virus particles suggests a non-lytic or abortive replication cycle in oligodendrocytes.
- This study provides insights into the mechanisms of viral-induced demyelination in the CNS.