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Interconnection between thyroid hormone signalling pathways and parvovirus cytotoxic functions
J M Vanacker1, V Laudet, G Adelmant
1Unité d'Oncologie Moléculaire, Institut Pasteur de Lille, Centre National de la Recherche Scientifique URA 1160, France.
Abstract:
Nonstructural (NS) proteins of autonomous parvoviruses can repress expression driven by heterologous promoters, an activity which thus far has not been separated from their cytotoxic effects. It is shown here that, in transient transfection assays, the NS-1 protein of the parvovirus minute virus of mice (MVMp) activates the promoter of the human c-erbA1 gene, encoding the thyroid hormone (T3) receptor alpha. The endogenous c-erbA1 promoter is also a target for induction upon MVMp infection. Moreover, T3 was found to up-modulate the level of cell sensitivity to parvovirus attack. These data suggest an interconnection between T3 signalling and NS cytotoxic pathways.
Insights
Minute virus of mice nonstructural protein 1 (NS-1) activates the human c-erbA1 gene promoter, suggesting a link between thyroid hormone (T3) signaling and parvovirus cytotoxicity. T3 also increases cell susceptibility to parvovirus infection.
Area of Science:
- Virology
- Molecular Biology
- Cell Biology
Background:
- Autonomous parvoviruses encode nonstructural (NS) proteins that can repress heterologous promoter expression.
- This NS protein activity has been inseparable from their cytotoxic effects.
Purpose of the Study:
- To investigate the interaction between parvovirus NS proteins and host cell gene promoters.
- To determine if the NS-1 protein of minute virus of mice (MVMp) affects the human c-erbA1 gene promoter.
- To explore the role of thyroid hormone (T3) signaling in parvovirus infection.
Main Methods:
- Transient transfection assays to assess promoter activity.
- MVMp infection of cells to study endogenous gene promoter regulation.
- Analysis of cell sensitivity to parvovirus following T3 modulation.
Main Results:
- MVMp NS-1 protein activates the promoter of the human c-erbA1 gene, which encodes the thyroid hormone (T3) receptor alpha.
- The endogenous c-erbA1 promoter is induced upon MVMp infection.
- T3 up-modulates cellular sensitivity to parvovirus infection.
Conclusions:
- The NS-1 protein's interaction with the c-erbA1 promoter is a novel finding, separating its transcriptional activity from cytotoxicity.
- These data reveal an interconnection between T3 signaling pathways and parvovirus NS protein-mediated cytotoxic effects.
- T3 signaling may influence host cell susceptibility to parvovirus, highlighting a potential new avenue for therapeutic intervention.