novobiocin and Cytomegalovirus-Infections

The effects of selected DNA repair inhibitors on the frequency of human cytomegalovirus (HCMV)-induced chromosome aberrations were evaluated in human peripheral blood lymphocytes (PBLs). Treatment of HCMV-infected PBLs with camptothecin (0.05 to 0.3 micrograms/ml), an inhibitor of topoisomerase I, for 30 hr resulted in a significant (P less than 0.01) synergistic enhancement of the frequency of HCMV-induced chromosome damage. On the other hand, a significant increase in the frequency of chromosome damage was not noted for infected PBLs treated with either 3-aminobenzamide (3-AB; 3 to 30 micrograms/ml), an inhibitor of poly(ADP-ribose) polymerase, or novobiocin (3 to 30 micrograms/ml), an inhibitor of topoisomerase II or excision repair processes, for 30 hr. Chromatid-type breaks and exchanges were the predominant type of chromosome aberrations observed in the HCMV-infected cells treated with camptothecin, suggesting that HCMV infection is associated with the induction of single-strand DNA breaks. Furthermore, these findings suggest that HCMV infection does not inflict direct DNA damage which is repaired through 3-AB- or novobiocin-sensitive pathways.

Topics: Benzamides; Camptothecin; Cells, Cultured; Chromosome Aberrations; Cytomegalovirus Infections; DNA Repair; Dose-Response Relationship, Drug; Humans; Lymphocytes; Novobiocin; Poly(ADP-ribose) Polymerase Inhibitors

.5 mM of novobiocin completely suppresses the replication of human cytomegalovirus (HCMV) in vitro. Based on the evidence that murine cytomegalovirus (MCMV) titres were reduced in vitro by 60% with the same concentration of the drug, the in vivo antiviral activity of novobiocin has been tested in the murine model. The results showed that if treatment started before the infection virus was not isolated from parenchymal organs during treatment. Virus could be isolated 24 h after stopping treatment, but not from kidney or spleen.

Topics: Animals; Cytomegalovirus; Cytomegalovirus Infections; Female; Mice; Mice, Inbred Strains; Novobiocin

Topics: Cytomegalovirus Infections; Humans; Idoxuridine; Infant, Newborn; Male; Novobiocin