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Use of Viral Entry Assays and Molecular Docking Analysis for the Identification of Antiviral Candidates against Coxsackievirus A16
Published on: July 15, 2019
Effect of lovastatin on coxsackievirus B3 infection in human endothelial cells
Bianca Werner1, Sven Dittmann, Carsten Funke
1Department of Cardiology, Heart and Diabetes Center NRW, Ruhr University of Bochum, Georgstr. 11, 32545, Bad Oeynhausen, NRW, Germany, bwerner@hdz-nrw.de.
Objective:
The coxsackie and adenovirus receptor (CAR) mediates the entry of coxsackievirus B (CVB) and adenovirus into host cells and is, therefore, a key determinant for the molecular pathogenesis of viral diseases such as myocarditis. The aim was to investigate the influence of HMG-CoA reductase inhibitor lovastatin on CAR expression in endothelial cells.
Methods:
Human umbilical vein endothelial cells (HUVECs) were exposed to different concentrations of lovastatin (0.05-5 μmol/l) for up to 48 h. Alterations in CAR expression were examined by quantitative real-time PCR (qRT-PCR) and flow cytometry. In addition, after treatment with 1 μmol/l lovastatin for 48 h, HUVECs were infected for 8 h with CVB3 and virus replication was detected by qRT-PCR using viral-specific TaqMan probes.
Results:
We found that lovastatin decreases CAR mRNA expression by up to 80% (p < 0.01) and CAR protein expression by up to 19% (p < 0.01), in a concentration-dependent manner. Moreover, virus replication of CVB3 was significantly inhibited after lovastatin treatment (p < 0.05). The signaling mechanism of CAR down-regulation by lovastatin depends on the Rac1/Cdc42 pathway.
Conclusion:
This study shows for the first time that lovastatin reduces the expression of CAR and subsequently the replication of CVB3 in HUVECs.
Insights
Lovastatin, a statin drug, reduces coxsackie and adenovirus receptor (CAR) expression in endothelial cells. This inhibition subsequently decreases coxsackie B virus 3 (CVB3) replication, offering potential therapeutic insights.
Area of Science:
- Molecular biology
- Virology
- Cardiovascular research
Background:
- The coxsackie and adenovirus receptor (CAR) is crucial for coxsackievirus B (CVB) and adenovirus entry into host cells.
- CAR plays a key role in the molecular pathogenesis of viral diseases, including myocarditis.
Purpose of the Study:
- To investigate the effect of HMG-CoA reductase inhibitor, lovastatin, on CAR expression in endothelial cells.
- To determine if lovastatin influences CVB3 replication in human umbilical vein endothelial cells (HUVECs).
Main Methods:
- HUVECs were treated with varying concentrations of lovastatin (0.05-5 μmol/l) for up to 48 hours.
- CAR expression was quantified using quantitative real-time PCR (qRT-PCR) and flow cytometry.
- CVB3 replication was assessed via qRT-PCR in lovastatin-treated HUVECs.
Main Results:
- Lovastatin significantly decreased CAR mRNA expression by up to 80% and CAR protein expression by up to 19% in a dose-dependent manner.
- Lovastatin treatment resulted in significant inhibition of CVB3 replication.
- The mechanism involves lovastatin-induced down-regulation of CAR via the Rac1/Cdc42 pathway.
Conclusions:
- Lovastatin reduces CAR expression in HUVECs.
- Lovastatin inhibits CVB3 replication in HUVECs, suggesting a potential therapeutic strategy for viral myocarditis.
Related Concept Videos
Lipid-Lowering Drugs: Statins and Miscellaneous Agents
Endocarditis III: Medical Management
Inhibitors of Viral Protein Synthesis
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Endocarditis I: Introduction
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