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Characterization of canine distemper viruses adapted to neural cells and their neurovirulence in mice
Abstract:
Interaction of the Onderstepoort strain of canine distemper virus (CDV) with three established human neural cells, i.e. IMR-32 neuroblastoma, 118-MGC glioma and KG-1 oligodendroglioma, was examined, and adaptation of CDV to these cells was also attempted. The unadapted virus was found to grow at relatively low titers in the three neural cells inducing moderate to minimal cytopathic effects (CPE). The virus was successfully grown at high titers in these cells after 8 to 10 passages. Biological characteristics such as growth rate, morphology of CPE and plaque size changed after adaptation. Analysis by SDS-polyacrylamide gel electrophoresis, however, failed to show any difference in the molecular weight of component proteins among the unadapted and three adapted viruses. Inbred DDD strain of mice developed clinical signs after intracerebral inoculation with the unadapted virus but most of them survived with histological lesions of encephalitis. Neuroblastoma-adapted virus induced only transient clinical signs in some animals with mild encephalitic lesions in the gray matter. Increases in neurovirulence were found for viruses adapted to glioma and oligodendroglioma cells. Almost all mice inoculated with these two viruses at 3 weeks of age died within 8 days with histological lesions consisting of hyperemia, edema, severe degeneration of nerve cells and a few giant cells. Demyelinating lesions in the absence of inflammatory changes were observed in the cerebellum, pons and medulla oblongata of animals inoculated with oligodendroglioma-adapted virus.
Insights
Canine distemper virus (CDV) adapted to human neural cells showed altered neurovirulence in mice. Glioma and oligodendroglioma-adapted CDV significantly increased mortality and induced severe lesions, including demyelination.
Area of Science:
- Virology
- Neuroscience
- Cell Biology
Background:
- Canine distemper virus (CDV) is a significant pathogen.
- Understanding CDV's interaction with neural cells is crucial for studying neuroinflammation and demyelination.
Purpose of the Study:
- To examine the interaction of CDV with human neural cell lines.
- To adapt CDV to these cell lines and assess changes in biological characteristics and neurovirulence.
Main Methods:
- In vitro culture of CDV with IMR-32 neuroblastoma, 118-MGC glioma, and KG-1 oligodendroglioma cells.
- Serial passage of CDV in these cell lines.
- SDS-polyacrylamide gel electrophoresis to analyze viral proteins.
- Intracerebral inoculation of mice with adapted and unadapted CDV.
Main Results:
- CDV adapted to high titers in all three neural cell lines after 8-10 passages, with altered growth rates, cytopathic effects, and plaque sizes.
- SDS-PAGE showed no changes in viral protein molecular weights.
- Unadapted CDV caused mild encephalitis in mice.
- Neuroblastoma-adapted CDV showed reduced neurovirulence.
- Glioma- and oligodendroglioma-adapted CDV significantly increased neurovirulence, causing high mortality and severe lesions, including demyelination in the oligodendroglioma-adapted group.
Conclusions:
- CDV can be adapted to human neural cell lines, altering its biological properties.
- Adaptation to glioma and oligodendroglioma cells enhances CDV neurovirulence.
- These findings provide insights into CDV-induced neurological disease and demyelination.