Effects of the epipodophyllotoxin VP-16-213 on herpes simplex virus type 2 replication.
It has been recently shown that VP-16-213, a semi-synthetic derivative of podophyllotoxin, inhibits the function of mammalian DNA topoisomerase II. In the present study, we examined the effects of VP-16-213 on the replication of herpes simplex virus type 2 (HSV-2). The compound did not inhibit the synthesis of early viral polypeptides at concentrations at which viral DNA synthesis was strongly suppressed, but induced double-strand breaks in newly synthesized HSV DNA. Electron microscopic examination of treated cells revealed the presence of a number of capsids with empty or partial cores. The level of topoisomerase II activity remained unaltered after infection, and all attempts to isolate VP-16-213-resistant mutants of HSV-2 have failed in spite of extensive efforts. It is suggested therefore that the mode of action of VP-16-213 may be inhibition of viral DNA synthesis by impairing the function of host cell topoisomerase II.
D000818:Animals; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects*; D004622:Embryo, Mammalian; D005047:Etoposide / Q000494:pharmacology*; D051379:Mice; D018139:Simplexvirus / Q000187:drug effects* / Q000235:genetics; D014779:Virus Replication / Q000187:drug effects
D005047:Etoposide