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Cytomegalovirus replication in murine microglial cell cultures: suppression of permissive infection by
1Dept. of Medicine, Hennepin County Medical Center, Minneapolis, MN 55415.
Abstract:
The pathogenesis of encephalitis due to cytomegalovirus (CMV), particularly the role of microglial cells in the spread or control of infection, remains incompletely defined. In this study, microglial cells were isolated from the brains of newborn mice and infected in vitro with murine CMV (MCMV). Microglial cells supported productive MCMV replication, and the MCMV-infected microglia manifested a cytopathic effect (CPE) characteristic of CMV infection. Exposure of microglia to interferon-gamma (IFN-gamma) 24 h before infection markedly suppressed virus production and resultant CPE in a dose-dependent fashion. Furthermore, the addition of IFN-gamma 2 h after infection demonstrated an antiviral effect equivalent to that achieved when IFN-gamma was administered 2 h before infection. These results demonstrate that murine microglial cells are fully permissive to MCMV replication and that IFN-gamma markedly suppresses virus expression in these cells.
Insights
Murine microglial cells support cytomegalovirus (CMV) replication. Interferon-gamma (IFN-gamma) effectively suppresses CMV infection in these cells, regardless of treatment timing, offering potential therapeutic insights.
Area of Science:
- Neuroimmunology
- Virology
- Cell Biology
Background:
- The role of microglial cells in cytomegalovirus (CMV) encephalitis pathogenesis is not fully understood.
- Investigating microglial cell permissiveness to CMV and their response to antiviral treatments is crucial.
Purpose of the Study:
- To determine if murine microglial cells are permissive to murine CMV (MCMV) infection.
- To evaluate the efficacy of interferon-gamma (IFN-gamma) in controlling MCMV replication in microglial cells.
Main Methods:
- Isolation of microglial cells from newborn mouse brains.
- In vitro infection of microglial cells with MCMV.
- Treatment of infected cells with varying doses and timings of IFN-gamma.
Main Results:
- Murine microglial cells support productive MCMV replication and exhibit cytopathic effects.
- IFN-gamma significantly suppressed MCMV production and cytopathic effects in a dose-dependent manner.
- IFN-gamma demonstrated antiviral efficacy when administered both before and after MCMV infection.
Conclusions:
- Murine microglial cells are fully permissive to MCMV replication.
- IFN-gamma is a potent suppressor of MCMV replication in microglial cells.
- IFN-gamma exhibits a robust antiviral effect against MCMV in microglia, irrespective of administration timing.