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Prevention of death in Semliki Forest virus-infected mice by administration of defective-interfering Semliki Forest
Abstract:
Adult mice inoculated with Semliki Forest virus (SFV) were protected from a lethal infection of the central nervous system by intranasal administration of defective-interfering (DI) SFV. DI SFV was prepared by eight passages at high m.o.i. in BHK 21 cells. Mice were treated with unpurified, unconcentrated tissue culture fluid which had been u.v.-irradiated to inactivate the infective virus present. Prevention of death was maximal when the DI virus was administered simultaneously with the infecting inoculum, and under the same conditions multiplication of infective virus in the brains of treated mice was reduced by 10(5)-fold. It was shown that DI SFV was propagated in mouse brains followed intranasal inoculation and it was concluded that protection was brought about through the intrinsic interfering capacity of the DI virus.
Insights
Intranasal administration of defective-interfering Semliki Forest virus (DI SFV) protected adult mice from lethal central nervous system infection. This protection was linked to the DI virus's inherent interfering capacity.
Area of Science:
- Virology
- Neuroscience
- Immunology
Background:
- Semliki Forest virus (SFV) causes lethal central nervous system infections.
- Defective-interfering (DI) viral particles possess the ability to interfere with the replication of standard viruses.
Purpose of the Study:
- To investigate the protective potential of intranasally administered defective-interfering Semliki Forest virus (DI SFV) against lethal SFV infection in the central nervous system.
- To elucidate the mechanism of protection conferred by DI SFV.
Main Methods:
- Adult mice were inoculated with a lethal dose of SFV.
- Mice received intranasal administration of u.v.-irradiated, unpurified DI SFV.
- DI SFV was prepared through high multiplicity of infection (m.o.i.) passages in BHK 21 cells.
- Viral replication in the brain was quantified.
Main Results:
- Intranasal administration of DI SFV significantly protected mice from lethal SFV-induced central nervous system infection.
- Protection was maximal when DI SFV was administered concurrently with the infecting SFV inoculum.
- A 10(5)-fold reduction in infective virus multiplication was observed in the brains of treated mice.
- DI SFV was shown to propagate within the mouse brain following intranasal inoculation.
Conclusions:
- Intranasal administration of DI SFV provides effective protection against lethal SFV encephalitis.
- The protective effect is attributed to the intrinsic viral interference mechanism of DI SFV.
- DI SFV can replicate in the brain, contributing to its therapeutic efficacy.