Machida H, Watanabe Y
Biology Laboratory, R & D Division, Yamasa Shoyu Co., Ltd, Chiba.
Microbiol Immunol. 1991;35(2):139-45. doi: 10.1111/j.1348-0421.1991.tb01541.x.
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.
将阿糖腺苷双戊酯(BV-araU)对感染水痘带状疱疹病毒(VZV)或单纯疱疹病毒1型(HSV-1)的人胚肺细胞中DNA合成的抑制作用与阿昔洛韦进行了比较。感染VZV或HSV-1可显著刺激细胞对[3H]胸苷的摄取及其掺入DNA,这表明掺入主要是由于病毒DNA合成。BV-araU和阿昔洛韦可剂量依赖性地抑制VZV感染细胞中的DNA合成,尽管在长时间用高浓度药物处理的细胞中[3H]胸苷的细胞摄取量有所下降。两种药物也均以剂量依赖性方式显著抑制HSV-1感染细胞中的DNA合成,且不影响细胞对[3H]胸苷的摄取。抑制DNA合成的药物浓度与其体外抗VZV和抗HSV-1活性密切相关。BV-araU对VZV感染细胞中DNA合成的抑制浓度是阿昔洛韦的千分之一。我们的结果表明,BV-araU对VZV和HSV-1的抗病毒作用基于对疱疹病毒感染细胞中DNA合成的抑制。