Abstract
Background/Purpose Inhibitory effects of statins on human immunodeficiency virus-1 or poliovirus replication were reported. Our aim was to clarify whether statins could inhibit the replication of cytomegalovirus (CMV) in human cells and to determine the changes in gene expression profiles in host cells treated with statins using a DNA microarray. Methods Human embryonic lung (HEL) fibroblast cells were infected with CMV (Towne strain) at a multiplicity of infection of 1 and were simultaneously treated with mevastatin, simvastatin, lovastatin, or pravastatin (0.001–10μM). HEL cells were incubated for 6 days, and progeny viral titers were quantified by plaque assay. Time-dependent effects of mevastatin or simvastatin (1μM) on CMV replication were also examined. We determined the effects of mevastatin or simvastatin at concentrations ranging from 0.1μM to 10μM on the expressions of CMV immediate-early-1 (IE-1) and late proteins using Western blotting. Comprehensive analysis of gene expression profiles in HEL cells treated with mevastatin (1μM) was performed with a DNA microarray 1 day after infection. Results The 50% effective concentration values for the inhibition of CMV titers by mevastatin, simvastatin, lovastatin, and pravastatin were 0.0006μM, 0.0055μM, 0.04μM, and 2.55μM, respectively. Inhibition of viral replication by mevastatin was observed when added 24 hours after infection, whereas that by simvastatin was observed when added 48 hours after infection. Mevastatin decreased the expression of the IE-1 protein, and simvastatin inhibited the expression of the late protein. We observed significant changes of cellular growth/differentiation-associated gene expressions (e.g., downregulated cdk2 mRNA) in HEL cells treated with mevastatin. Conclusion Our data suggest that treatment with mevastatin could inhibit CMV replication at IE phase through altered expressions of cellular growth/differentiation-associated genes.
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