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Attempts to detect homologous autointerference in vivo with influenza virus and vesicular stomatitis virus
Abstract:
Von Magnus particles of influenza virus and defective interfering T particles of vesicular stomatitis virus were unable to provide significant protection of mice from disease or death when inoculated intranasally or intracerebrally along with moderate or high doses of homologous infectious challenge virus. However, yields of infectious virus from the affected organs were reduced as compared to controls inoculated with infectious virus alone. Serial intracerebral passage of vesicular stomatitis virus in mouse brain at high doses failed to produce T particles detectable by in vitro autointerference assays on BHK(21) cells, whether or not T particles were introduced along with B virions at the first passage. When very low challenge doses of infectious B virions were inoculated intracerebrally along with high doses of homologous defective particles, there was significant prolongation of life, although most mice died eventually of slowly progressing disease. Also, the virus yields in the brains of these mice were significantly reduced, and virus was no longer detectable in the brains of "protected" mice surviving for 10 days or more. Our results suggest that although homologous autointerference does occur in vivo, it is a more complex phenomenon than in vitro cell culture experiments might indicate.
Insights
Defective virus particles like Von Magnus particles and T particles offered limited protection against homologous infectious virus in mice. However, they did reduce viral loads in organs, suggesting complex in vivo autointerference.
Area of Science:
- Virology
- Immunology
- Infectious Diseases
Background:
- Defective interfering particles (DIPs) are viral mutants that require a standard homologous virus for replication.
- DIPs are known to interfere with standard virus replication in vitro through autointerference.
- The in vivo efficacy of DIPs in protecting against homologous virus challenge remains incompletely understood.
Purpose of the Study:
- To investigate the protective capacity of Von Magnus particles (influenza virus) and T particles (vesicular stomatitis virus) against homologous infectious virus in a mouse model.
- To assess the impact of these defective particles on viral replication and disease progression in vivo.
- To explore the phenomenon of homologous autointerference in a living organism.
Main Methods:
- Mice were inoculated with defective virus particles and varying doses of homologous infectious virus via intranasal or intracerebral routes.
- Viral yields from affected organs were quantified to assess replication.
- Serial intracerebral passage of vesicular stomatitis virus was performed to detect T particle generation.
- Survival rates and disease progression were monitored in challenged mice.
Main Results:
- Defective particles did not provide significant protection against disease or death at moderate to high infectious virus doses.
- However, defective particles significantly reduced infectious virus yields in affected organs compared to controls.
- Inoculation with very low infectious virus doses alongside high doses of defective particles led to prolonged survival and reduced viral loads, with some mice clearing the virus.
- Serial passage experiments did not readily generate detectable T particles in vivo.
Conclusions:
- Homologous autointerference occurs in vivo but is more complex than observed in vitro.
- Defective virus particles can modulate viral pathogenesis and reduce viral loads in vivo, even without complete protection.
- Further research is needed to elucidate the mechanisms of in vivo autointerference and its therapeutic potential.