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Prolonged replication in the mouse central nervous system of reoviruses isolated from persistently infected cell
L A Morrison1, B N Fields, T S Dermody
1Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115.
Abstract:
We examined pathogenic characteristics of plaque-purified reoviruses isolated from persistently infected L-cell cultures (PI viruses) after intracranial inoculation into newborn mice. The PI viruses were isolated from independent cultures initiated with high-passage stocks of the wild-type (wt) strain, type 3 Dearing. The virulence of most PI viruses was equivalent to that of the wt strain. However, replication of PI viruses in the central nervous system of infected mice was prolonged to 25 (but not 50) days postinoculation. Thirty-eight percent (n = 186) of mice inoculated with the PI viruses had residual virus detectable in brain tissue 25 days after inoculation, in contrast to only 16% (n = 57) of mice inoculated with wt virus (P = 0.009). Mean residual brain titers were more than 20-fold higher in mice inoculated with PI viruses compared with wt virus (4.3 x 10(4) versus 2.1 x 10(3); P = 0.006). Tropism of PI virus within the brain resembled that of wt virus, and the distribution of PI virus antigen in the brain did not change over time. The extent of necrosis in the brains of mice harboring PI virus 25 days after inoculation was minimal, despite continued presence of high titers of infectious virus. The latter observation resembles the absence of cytopathicity seen in L-cell cultures persistently infected with reovirus. These observations suggest that the interaction of PI viruses with cells can be altered in vivo as well as in cell culture, but virus is eventually cleared from the infected animal.
Insights
Persistently infected (PI) reoviruses showed prolonged replication in mouse brains compared to wild-type strains. Despite high virus titers, PI reovirus infection caused minimal brain necrosis, suggesting altered in vivo cell interactions.
Area of Science:
- Virology
- Neuroscience
- Infectious Diseases
Background:
- Reoviruses are double-stranded RNA viruses known to cause various infections.
- Persistent viral infections can alter virus-host interactions.
- Understanding reovirus pathogenesis is crucial for managing viral diseases.
Purpose of the Study:
- To investigate the pathogenic characteristics of reoviruses isolated from persistently infected L-cell cultures (PI viruses).
- To compare the in vivo behavior of PI reoviruses with wild-type (wt) reoviruses in a mouse model.
- To assess the impact of PI reovirus infection on the central nervous system.
Main Methods:
- Intracranial inoculation of newborn mice with plaque-purified PI reoviruses and wt reoviruses (type 3 Dearing).
- Monitoring of virus replication, distribution, and antigen presence in the central nervous system over time.
- Histopathological examination of brain tissue to assess necrosis and cytopathic effects.
Main Results:
- PI reoviruses exhibited prolonged replication in the mouse central nervous system (up to 25 days post-inoculation).
- A significantly higher percentage of mice inoculated with PI reoviruses had detectable brain virus at 25 days compared to wt virus.
- Despite high infectious virus titers, PI reovirus infection resulted in minimal brain necrosis, similar to observations in persistently infected cell cultures.
Conclusions:
- PI reoviruses demonstrate altered in vivo interactions with host cells, leading to prolonged central nervous system replication without significant cytopathology.
- These findings suggest that persistent reovirus infections can modulate viral pathogenesis.
- Reovirus is eventually cleared from the infected animal despite prolonged CNS presence.