SODIUM VALPROATE, AN ANTICONVULSANT DRUG, STIMULATES HUMAN CYTOMEGALOVIRUS REPLICATION

Valproic acid (VPA), a simple branched-chain fatty acid having anticon vulsant activity and used in the treatment of many forms of epilepsy, markedly stimulated human cytomegalovirus (HCMV) replication in human fibroblasts (MRC-5 cells). The maximum level of stimulation was reache d when cells were treated for 24 h before infection. The enhancement o f virus replication correlated with an increase in the number of immed iate early (IE) and early (E) antigen-positive cells. VPA also induced expression of IE antigens after transfection of fibroblasts with a pl asmid containing the entire IE1-2 region. Moreover, VPA stimulated the HCMV IE1-2 promoter/enhancer-mediated expression of beta-galactosidas e in a stably transfected Jurkat T cell line. Recently, VPA was shown to inhibit glutathione reductase in human red blood cells, but an acti on through the glutathione metabolic pathway can be eliminated in this case, since VPA decreased the intracellular level of glutathione in J urkat T cells but not in MRC-5 cells. The ability of VPA to stimulate HCMV replication provides an attractive model for studying the molecul ar mechanism of the regulation of HCMV IE1-2 gene expression.