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Macrophage Cholesterol Depletion and Its Effect on the Phagocytosis of Cryptococcus neoformans
Published on: December 19, 2014
Cholesterol depletion affects infectivity and stability of pseudorabies virus
Ann S Desplanques1, Maria Pontes, Natasha De Corte
1Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, Merelbeke, Belgium.
Abstract:
Statins, such as lovastatin, inhibit the cellular cholesterol biosynthesis. Addition of lovastatin to SK cells and subsequent infection with the alphaherpesvirus pseudorabies virus (PRV) did not affect the intracellular production of viral structural proteins but reduced virus titers. Addition of methyl-beta-cyclodextrin to deplete cholesterol from the viral envelope also resulted in reduced virus titers. Addition of exogenous cholesterol restored virus titers in both experimental assays. Further analysis showed that reducing cholesterol levels reduced both the infectivity of newly produced infectious virus and their stability, as assessed by determining virus titers immediately after treatment or upon storage of the virus at room temperature or frozen. This is the first report to demonstrate that cholesterol is involved in the stability of infectious alphaherpesvirus, and that treatment of host cells with statins reduces alphaherpesvirus titers. Hence, cholesterol is important for pseudorabies virus infectivity and stability.
Insights
Statins reduce cholesterol, which is vital for pseudorabies virus (PRV) infectivity and stability. Lowering cholesterol in host cells or viral envelopes decreases PRV titers, while adding cholesterol restores them.
Area of Science:
- Virology
- Biochemistry
- Cell Biology
Background:
- Statins are drugs that inhibit cholesterol biosynthesis.
- Alphaherpesviruses, like pseudorabies virus (PRV), are significant pathogens.
- The role of cholesterol in viral stability and infectivity is an area of ongoing research.
Purpose of the Study:
- To investigate the impact of cholesterol depletion on pseudorabies virus (PRV) infectivity and stability.
- To determine if statin treatment affects PRV titers.
- To elucidate the role of cholesterol in the alphaherpesvirus life cycle.
Main Methods:
- SK cells were treated with lovastatin (a statin) or methyl-beta-cyclodextrin to deplete cholesterol.
- Cells were infected with PRV, and viral structural protein production and virus titers were assessed.
- Exogenous cholesterol was added to evaluate its effect on virus titers.
- Infectivity and stability of PRV were assessed after cholesterol depletion and replenishment.
Main Results:
- Statin treatment and cholesterol depletion reduced PRV titers without affecting viral protein production.
- Reduced cholesterol levels decreased both the infectivity and stability of newly produced PRV.
- Addition of exogenous cholesterol restored virus titers in cholesterol-depleted conditions.
Conclusions:
- Cholesterol is crucial for the infectivity and stability of infectious alphaherpesvirus.
- Statin treatment of host cells can reduce alphaherpesvirus titers by impacting cholesterol levels.
- This study highlights cholesterol as a key factor in PRV infectivity and stability, suggesting potential therapeutic targets.
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