Effect of 2-deoxy-D-glucose on cytomegalovirus-induced DNA synthesis in human fibroblasts.
2-Deoxy-D-glucose (dGlc) was found to selectively inhibit virus DNA synthesis in human embryonic lung cells infected with human cytomegalovirus (HCMV). The effective concentration of dGlc was approx. 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. Virus DNA synthesis could be selectively inhibited by addition of dGlc even after initiation of HCMV DNA replication. In contrast, virus DNA synthesis in herpes simplex virus-infected cells was insensitive to dGlc. The drug was found to deplete HCMV-infected cells of uridine triphosphate 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 analysed. In contrast to preparations of untreated or phosphonoacetic acid (PAA)-treated, HCMV-infected cells, those of dGlc-treated cells lacked significant in vitro DNA-synthesizing activity; virus DNA was not synthesized by these preparations. Tunicamycin in the presence of low concentrations of dimethyl sulphoxide was also found to be effective in abolishing HCMV-induced DNA replication. It is thus suggested that dGlc interferes with the function of an 'early' chromatin-associated glycoprotein essential for virus DNA synthesis.
D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D003587:Cytomegalovirus / Q000254:growth & development / Q000378:metabolism*; D004279:DNA, Viral / Q000096:biosynthesis*; D003837:Deoxy Sugars / Q000494:pharmacology*; D003847:Deoxyglucose / Q000494:pharmacology*; D005347:Fibroblasts; D005944:Glucosamine / Q000494:pharmacology; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism; D018139:Simplexvirus / Q000378:metabolism; D014529:Uridine / Q000378:metabolism
D002843:Chromatin; D004279:DNA, Viral; D003837:Deoxy Sugars; D012333:RNA, Messenger; D003847:Deoxyglucose; D005944:Glucosamine; D014529:Uridine