Mancini W R, De Clercq E, Prusoff W H
J Biol Chem. 1983 Jan 25;258(2):792-5.
E-5-(2-Bromovinyl)-2'-deoxyuridine (BrvdUrd) produced a dose-dependent shift in the density of herpes simplex virus type 1 (HSV-1) DNA at concentrations which yielded potent inhibition of virus replication in cultured Vero cells. Although the density of cellular DNA was not altered by these concentrations of BrvdUrd, incorporation of this analogue into cellular DNA of HSV-1-infected cells has been previously observed in this laboratory. The degree of inhibition correlated with the amount of BrvdUrd substituted for thymidine in HSV-1 DNA. BrvdUrd-substituted DNA was more labile as determined by a dose-dependent increase in single strand breaks when examined by centrifugation in alkaline sucrose gradients. Thus, the potent antiviral action of BrvdUrd observed in cell culture correlates not only with its incorporation into HSV-1 DNA but also with an altered stability of this DNA.
E-5-(2-溴乙烯基)-2'-脱氧尿苷(BrvdUrd)在一定浓度下可使单纯疱疹病毒1型(HSV-1)DNA的密度发生剂量依赖性变化,该浓度能有效抑制病毒在培养的非洲绿猴肾细胞(Vero细胞)中的复制。尽管这些浓度的BrvdUrd不会改变细胞DNA的密度,但此前在本实验室已观察到该类似物可掺入HSV-1感染细胞的细胞DNA中。抑制程度与HSV-1 DNA中被BrvdUrd取代的胸腺嘧啶的量相关。通过碱性蔗糖梯度离心检测发现,BrvdUrd取代的DNA更不稳定,单链断裂呈剂量依赖性增加。因此,在细胞培养中观察到的BrvdUrd的强效抗病毒作用不仅与其掺入HSV-1 DNA有关,还与其DNA稳定性的改变有关。