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Analysis of Theiler's virus isolates from persistently infected mouse nervous tissue
Abstract:
The DA strain of Theiler's virus causes a chronic progressive demyelination in mice following intracerebral inoculation. Virus was isolated from chronically infected mice, and then grown in cell culture, and the isolates were compared with the parent virus used for inoculation. No defective interfering particles or temperature-sensitive virus were recovered, and capsid proteins appeared identical by SDS-PAGE. One of three isolates had evidence of genomic mutation by Tl ribonuclease oligonucleotide fingerprinting. The significance of these findings with regard to the generation and maintenance of persistence and to adaptation to cell culture is discussed. Also of interest was the marked difference between the DA fingerprint and that of GD VII, a serologically related strain with different biological activity.
Insights
Theiler
Area of Science:
- Virology
- Neuroscience
- Immunology
Background:
- Theiler's virus (TMEV) DA strain induces chronic demyelination in mice.
- Understanding viral persistence mechanisms is crucial for neurodegenerative disease research.
Purpose of the Study:
- To investigate viral genomic changes during chronic Theiler's virus infection in mice.
- To compare cell culture-adapted isolates with the parent virus.
Main Methods:
- Intracerebral inoculation of mice with TMEV DA strain.
- Virus isolation from infected mouse brains and subsequent cell culture.
- Analysis of viral capsid proteins using SDS-PAGE.
- Genomic mutation analysis via T1 ribonuclease oligonucleotide fingerprinting.
Main Results:
- No defective interfering particles or temperature-sensitive mutants were recovered.
- Capsid proteins of isolates were identical to the parent virus.
- One of three isolates showed genomic mutation by oligonucleotide fingerprinting.
- Significant genomic differences were observed between DA and GD VII strains.
Conclusions:
- Viral persistence in the central nervous system may involve subtle genomic mutations.
- Adaptation to cell culture did not yield major changes in capsid proteins or defective particles.
- Oligonucleotide fingerprinting is a sensitive method for detecting genomic alterations in TMEV.