Inhibition of DNA synthesis in varicella-zoster virus-infected cells by BV-araU.
The inhibitory effect of BV-araU on DNA synthesis in human embryonic lung cells infected with varicella-zoster virus (VZV) or herpes simplex virus type 1 (HSV-1) was compared with that of acyclovir. Cellular uptake of [3H]thymidine and its incorporation into DNA was markedly stimulated by the infection with VZV or HSV-1, suggesting that the incorporation was mainly due to viral DNA synthesis. DNA synthesis in VZV-infected cells was dose-dependently suppressed by BV-araU and acyclovir, although cellular uptake of [3H]thymidine decreased in cells treated with a high concentration of drugs for an extended time. DNA synthesis in HSV-1-infected cells was also markedly inhibited by both drugs in a dose-dependent manner, without affecting cellular uptake of [3H]thymidine. The concentration of drugs inhibiting DNA synthesis was well correlated to their in vitro anti-VZV and anti-HSV-1 activities. The inhibitory concentration of BV-araU for DNA synthesis in VZV-infected cells was one-thousandth of that of acyclovir. Our results suggest that the antiviral action of BV-araU against VZV and HSV-1 is based on the inhibition of DNA synthesis in herpesvirus-infected cells.
Machida
H
H
Biology Laboratory, R & D Division, Yamasa Shoyu Co., Ltd, Chiba.
Watanabe
Y
Y
D000212:Acyclovir / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology*; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D004279:DNA, Viral / Q000096:biosynthesis* / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000382:microbiology; D014645:Herpesvirus 3, Human / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D008168:Lung / Q000382:microbiology; D018139:Simplexvirus / Q000187:drug effects / Q000254:growth & development; D013936:Thymidine / Q000378:metabolism
D000998:Antiviral Agents; D004279:DNA, Viral; D001086:Arabinofuranosyluracil; C031368:sorivudine; D013936:Thymidine; D000212:Acyclovir