Effect of 2-Deoxy-D-Glucose on Cytomegalovirus-induced DNA Synthesis in Human Fibroblasts

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Abstract
2-Deoxy-D-glucose (dGlc) selectively inhibited virus DNA synthesis in human embryonic lung cells infected with human cytomegalovirus (HCMV). The effective concentrations of dGlc was .apprx. 10-fold higher in culture medium containing glucose instead of sodium pyruvate. This inhibitory action of dGlc was fully reversible following replacement of the inhibitor medium by fresh medium after a 48 h treatment of infected cells. Viral DNA synthesis could be selectively inhibited by addition of dGlc even after initiation of HCMV DNA replication. Viral DNA synthesis in herpes simplex virus-infected cells was insensitive to dGlc. The drug depleted HCMV-infected cells of UTP and caused a progressive reduction of uridine incorporation into RNA. To substantiate a possible interference by dGlc with the expression and/or function of virus-induced, chromatin-associated factors essential for virus DNA replication, DNA synthesis of chromatin preparations from dGlc-treated, HCMV-infected cells was analyzed. In contrast to preparations of untreated or phosphonoacetic acid-treated, HCMV-infected cells, those of dGlc-treated cells lacked significant in vitro DNA-synthesizing activity; viral DNA was not synthesized by these preparations. Tunicamycin in the presence of low concentrations of dimethyl sulfoxide was also found to be effective in abolishing HCMV-induced DNA replication. Thus, dGlc probably interferes with the function of an early chromatin-associated glycoprotein essential for virus DNA synthesis.