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The ionophore monensin inhibits mouse polyomavirus DNA replication and destabilizes viral early mRNAs
A Iacoangeli1, G Melucci-Vigo, G Risuleo
1Dipartimento di Genetica e Biologia Molecolare, Università La Sapienza, Rome, Italy.
Abstract:
Monensin is a ionophore compound with different biological activities. It raises the intralysosomal pH, it binds the plasma membranes particularly at the level of the cisternal system of the Golgi apparatus. It causes imbalance in the intramembrane ion traffic and inhibits export of secretory proteins at membrane level. Monensin blocks endocytosis and therefore impedes entry of toxic molecules. The drug also inhibits viral proliferation of RNA and DNA viruses such as vesicular stomatitis, influenza and human polyomaviruses. In this report we show that monensin effectively abolishes viral DNA replication of mouse polyomavirus. Results show that the half life of viral early mRNAs is significantly reduced in the presence of the drug. Therefore we suggest that the reduction of viral DNA synthesis is a consequence of the reduced intranuclear pool of viral early antigens.
Insights
Monensin, an ionophore, inhibits viral DNA replication by reducing viral early messenger RNA stability. This leads to decreased viral early antigens and halts viral DNA synthesis in mouse polyomavirus.
Area of Science:
- Biochemistry
- Virology
- Cell Biology
Background:
- Monensin is an ionophore compound with diverse biological activities.
- It affects intracellular pH, membrane transport, and protein secretion.
- Monensin is known to inhibit the proliferation of various RNA and DNA viruses.
Purpose of the Study:
- To investigate the effect of monensin on viral DNA replication.
- To determine the impact of monensin on viral early messenger RNA (mRNA) stability.
- To elucidate the mechanism by which monensin inhibits mouse polyomavirus DNA synthesis.
Main Methods:
- Treatment of mouse polyomavirus-infected cells with monensin.
- Analysis of viral DNA replication.
- Measurement of viral early mRNA half-life using quantitative techniques.
Main Results:
- Monensin effectively abolished viral DNA replication of mouse polyomavirus.
- The half-life of viral early mRNAs was significantly reduced in the presence of monensin.
- A reduced intranuclear pool of viral early antigens was observed.
Conclusions:
- Monensin inhibits mouse polyomavirus DNA synthesis.
- The reduction in viral DNA synthesis is attributed to decreased viral early mRNA stability.
- This leads to a diminished pool of viral early antigens, ultimately halting viral DNA replication.