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Updated: Aug 15, 2026
Viral Tracing of Genetically Defined Neural Circuitry
Published on: October 17, 2012
Different pathogenicity of encephalitic togaviruses in organotypic cultures of spinal cord slices
1Department of Virology, Israel Institute for Biological Research Ness-Ziona.
Abstract:
The pathogenicity of two encephalitic Togaviruses, Sindbis virus (SV), an alphavirus, and West Nile virus (WNV), a flavivirus, was studied in organotypic cultures of fetal mouse spinal cord slices grown in roller tubes. After about 3 weeks in vitro, during which time the cultures became abundantly myelinated, they were infected either by 5 X 10(5) PFU SV or by 5 X 10(6) PFU WNV per culture. The viruses caused different patterns of cytopathogenicity: SV induced severe cytotoxicity in all glia cells and neurons with concomitant demyelination within 48 hr. In contrast, WNV, even 4 days after infection, caused only mild cytopathic effects mainly to neurons and astrocytes and a slight degree of damage to the myelin sheath. A most remarkable finding was the entrapment of WNV particles in the interperiod lines of the myelin sheaths. Treatment of cultures with mouse alpha and beta interferon prior to their infection with either virus protected the cultures from any viral damage. Long-term exposure of non-infected control organotypic cultures of fetal spinal cord slices to mouse interferons had no significant effect on neuronal and glial differentiation, and myelin formation.
Insights
Sindbis virus (SV) caused rapid, severe damage to spinal cord cultures, while West Nile virus (WNV) showed milder effects and unique myelin sheath entrapment. Interferon protected cultures from both viral infections.
Area of Science:
- Neurovirology
- Immunology
- Cell Biology
Background:
- Togaviruses, including Sindbis virus (SV) and West Nile virus (WNV), are significant causes of encephalitis.
- Organotypic cultures of fetal mouse spinal cord slices provide a model for studying viral neuroinflammation and demyelination.
Purpose of the Study:
- To compare the pathogenicity of SV and WNV in myelinated organotypic spinal cord cultures.
- To investigate the protective effects of interferons against these viral infections.
Main Methods:
- Organotypic cultures of fetal mouse spinal cord slices were established and myelinated in vitro.
- Cultures were infected with SV or WNV, and cytopathogenicity was assessed.
- Interferon treatment was applied before viral infection to evaluate protective effects.
Main Results:
- SV induced rapid, severe cytotoxicity in neurons and glia, leading to demyelination within 48 hours.
- WNV caused milder neuronal and astrocyte damage with slight myelin damage, and WNV particles were found within myelin sheaths.
- Pre-treatment with mouse alpha and beta interferon completely protected cultures from viral-induced damage.
Conclusions:
- SV and WNV exhibit distinct neuropathogenic mechanisms in the central nervous system.
- Interferons are effective in preventing Togavirus-induced neurodegeneration and demyelination.
- Organotypic spinal cord cultures are a valuable model for studying viral encephalitis and potential therapeutic interventions.
