Measles virus-specific dsRNAs are targets for unwinding/modifying activity in neural cells in vitro
A Ecker1, V ter Meulen, K Baczko
1Institute for Virology and Immunobiology, Würzburg, Germany.
Abstract:
Biased hypermutation events found predominantly in the matrix gene of measles virus isolated from persistent human CNS infections have been attributed to the action of a cellular unwinding/modifying activity (UMA). To define the level and distribution of this activity in brain cells, fractionated extracts were prepared from the nuclei and cytoplasm of human glioblastoma (D-54, U-251) and neuroblastoma (IMR-32, SKN-MC) cells and analyzed for their ability to modify synthetic dsRNAs specific for the measles virus (MV) matrix (M) gene. On a quantitative basis we could show that the activity localized to both the nuclear and cytoplasmic compartments of both cell types analyzed independent of cell proliferation. The presence of significant levels of UMA in the cytoplasm of human brain cells following growth arrestment in vitro with retinoic acid supports the interpretation that UMA may contribute to the attenuation of MV gene functions during the primary infection of brain cells, thereby supporting the establishment of virus persistence.
Insights
Cellular unwinding/modifying activity (UMA) in human brain cells modifies measles virus (MV) matrix gene dsRNA. This activity, found in both nuclear and cytoplasmic compartments, may contribute to persistent MV infections in the central nervous system (CNS).
Area of Science:
- Virology
- Neuroscience
- Molecular Biology
Background:
- Biased hypermutation in the measles virus (MV) matrix gene is observed in persistent human central nervous system (CNS) infections.
- This phenomenon is linked to a cellular unwinding/modifying activity (UMA).
Purpose of the Study:
- To determine the presence and location of UMA within human brain cells.
- To investigate the role of UMA in measles virus persistence in the CNS.
Main Methods:
- Preparation of fractionated nuclear and cytoplasmic extracts from human glioblastoma and neuroblastoma cell lines.
- Analysis of UMA's ability to modify synthetic double-stranded RNAs (dsRNAs) specific to the MV matrix (M) gene.
Main Results:
- UMA was detected in both nuclear and cytoplasmic compartments of all analyzed human brain cell types.
- The activity level was independent of cell proliferation.
- Significant UMA levels were found in cytoplasm after retinoic acid-induced growth arrest.
Conclusions:
- UMA is present in both nuclear and cytoplasmic fractions of human brain cells.
- UMA's localization and activity suggest a role in modulating MV gene function during initial brain infection.
- This modulation by UMA may facilitate the establishment of persistent measles virus infections in the CNS.
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