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Quercetinase pirin makes poliovirus replication resistant to flavonoid quercetin
Nickolay Neznanov1, Anna Kondratova, Konstantin M Chumakov
1Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. neznann@ccf.org
Abstract:
Flavonoid quercetin and its derivative, methylquercetin, inhibit the replication of poliovirus in several cell lines. Here, we show that replication of poliovirus is inhibited by quercetin and that the extent of this inhibition depends on the intracellular content of pirin, a quercetinase. HeLa cells contain higher content of pirin protein than normal kidney human epithelial (NKE) or 293 cells do. Poliovirus replication in HeLa cells is significantly more resistant to quercetin than its replication in NKE and 293 cells. Overexpression of pirin reduced antiviral inhibitory effect of quercetin, while siRNA-induced suppression of pirin level made poliovirus replication more sensitive to the flavonoid. The results suggest that quercetinase activity of pirin determines the resistance of poliovirus infection to quercetin.
Insights
The flavonoid quercetin inhibits poliovirus replication, with pirin protein levels determining cellular resistance. Higher pirin content in HeLa cells makes poliovirus more resistant to quercetin
Area of Science:
- Virology
- Biochemistry
- Cell Biology
Background:
- Flavonoids, including quercetin, exhibit antiviral properties.
- Poliovirus replication is a significant public health concern.
- Cellular factors influencing antiviral drug efficacy require further investigation.
Purpose of the Study:
- To investigate the role of pirin, a quercetinase, in quercetin's inhibition of poliovirus replication.
- To determine how intracellular pirin levels affect cellular resistance to poliovirus infection.
Main Methods:
- Comparing poliovirus replication inhibition by quercetin in different cell lines (HeLa, NKE, 293) with varying pirin content.
- Overexpressing pirin in cells to assess its impact on quercetin's antiviral effect.
- Using siRNA to suppress pirin levels and evaluate changes in quercetin sensitivity.
Main Results:
- Quercetin effectively inhibits poliovirus replication across tested cell lines.
- Intracellular pirin content directly correlates with cellular resistance to quercetin's antiviral effects.
- HeLa cells, with higher pirin levels, demonstrate greater resistance to quercetin compared to NKE and 293 cells.
- Pirin overexpression reduced quercetin's inhibitory effect, while pirin suppression enhanced sensitivity.
Conclusions:
- Pirin's quercetinase activity is a key determinant of cellular resistance to quercetin-mediated poliovirus inhibition.
- Targeting pirin levels could potentially modulate the efficacy of quercetin as an antiviral agent against poliovirus.
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