Specific and non-specific inhibition of CMV by a phosphorothioate oligonucleotide targeted to the pac-1 region of the a-sequence

Abstract

We have found previously that statins block human cytomegalovirus (HCMV) replication in human embryonic lung fibroblast (HEL) cells with reduced levels of viral immediate–early 1 (IE1) protein. To explore the mechanisms involved in inhibition by statins, we investigated the effects of statins on IE1 protein expression.In transient transfection experiments using a reporter plasmid carrying a luciferase gene under control of HCMV major immediate–early enhancer/promoter (MIEP), the statins had no effect on the MIEP activity in HEL cells. In U373-IE1 cells established by transfection with the IE1 gene driven by the MIEP into astrocytoma U373-MG cells, which are permissive for HCMV infection, the presence of statins did not affect IE1 protein expression. To investigate the difference in results between virus-infected and gene-transfected cells, we used UV-irradiated HCMV, which is capable only of binding to and internalizing in the cells. The experiments with UV-irradiated HCMV demonstrated that statins decreased IE1 protein expression in U373-IE1 cells infected with UV-inactivated virus.Virus-host responses triggered by UV-irradiated HCMV particle binding and penetration, occurring at an early stage of infection, might contribute to the inhibition of IE1 protein expression by statins.