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.
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