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Spontaneous and differentiation-dependent regulation of measles virus gene expression in human glial cells
S Schneider-Schaulies1, J Schneider-Schaulies, M Bayer
1Institut für Virologie und Immunbiologie, Universität Würzburg, Germany.
Abstract:
The expression of measles virus (MV) in six different permanent human glioma cell lines (D-54, U-251, U-138, U-105, U-373, and D-32) was analyzed. Although all cell lines were permissive for productive replication of all MV strains tested, U-251, D-54, and D-32 cells spontaneously revealed restrictions of MV transcription similar to those observed for primary rat astroglial cells and brain tissue. In vitro differentiation of D-54 and U-251 cells by substances affecting the intracellular cyclic AMP level caused a significant reduction of the expression of the viral proteins after 18, 72, and 144 h of infection. This pronounced restriction was not paralleled to a comparable level by an inhibition of the synthesis and biological activity in vitro of virus-specific mRNAs as shown by quantitative Northern (RNA) blot analyses and in vitro translation. The block in viral protein synthesis could not be attributed to the induction of type I interferon by any of the substances tested. Our findings indicate that down-regulation of MV gene expression in human brain cells can occur by a cell type-dependent regulation of the viral mRNA transcription and a differentiation-dependent regulation of translation, both of which may be crucial for the establishment of persistent MV infections in the central nervous system.
Insights
Measles virus (MV) expression in human glioma cells shows cell-type-specific transcriptional restrictions. Differentiation reduces viral protein synthesis, impacting persistent central nervous system infections.
Area of Science:
- Neurovirology
- Cell Biology
Background:
- Measles virus (MV) can establish persistent infections in the central nervous system (CNS).
- Understanding MV gene expression regulation in brain cells is crucial for deciphering persistent infection mechanisms.
Purpose of the Study:
- To analyze MV expression in human glioma cell lines.
- To investigate the impact of in vitro differentiation on MV gene expression and protein synthesis.
Main Methods:
- Analysis of MV replication and transcription in six human glioma cell lines.
- In vitro differentiation of specific cell lines using cyclic AMP-modulating agents.
- Quantitative Northern (RNA) blot analyses and in vitro translation assays.
- Assessment of type I interferon induction.
Main Results:
- All tested glioma cell lines supported productive MV replication.
- Specific cell lines (U-251, D-54, D-32) exhibited restricted MV transcription.
- In vitro differentiation significantly reduced viral protein expression.
- The reduction in protein synthesis was not fully explained by decreased viral mRNA levels.
- Type I interferon induction was not responsible for the observed protein synthesis block.
Conclusions:
- MV gene expression in human brain cells is regulated by cell type-dependent transcriptional control.
- Differentiation-dependent translational regulation also plays a role in controlling MV protein synthesis.
- These regulatory mechanisms are important for the establishment of persistent MV infections in the CNS.