Bernaerts R, Desgranges C, De Clercq E
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
Biochem Pharmacol. 1989 Jun 15;38(12):1955-61. doi: 10.1016/0006-2952(89)90494-2.
(E)-5-(2-Bromovinyl)uridine (BVUrd), the riboside counterpart of (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVdUrd), effected a dose-dependent inhibition of viral progeny formation and viral DNA synthesis in herpes simplex virus type 1 (HSV-1, strain KOS)-infected human (E6SM) diploid fibroblast cells. BVUrd was directly phosphorylated in HSV-1-infected cells, presumably by the virus-encoded thymidine kinase (TK), since (i) BVUrd was not phosphorylated by extracts of cells infected with a HSV-1 strain deficient in TK expression and (ii) the phosphorylation was inhibited by a polyclonal anti-HSV-1 antibody. Within the HSV-1-infected cells, BVUrd was incorporated into the viral DNA as BVdUMP (BVdUrd 5'-monophosphate). This incorporation may account for the antiviral action of BVUrd, and implies that, following its initial phosphorylation by the viral TK, BVUrd is converted to its 2'-deoxy counterpart, most likely at the 5'-diphosphate level (BVUDP----BVdUDP).
（E）-5-（2-溴乙烯基）尿苷（BVUrd）是（E）-5-（2-溴乙烯基）-2'-脱氧尿苷（BVdUrd）的核糖核苷类似物，对单纯疱疹病毒1型（HSV-1，KOS株）感染的人（E6SM）二倍体成纤维细胞中的病毒子代形成和病毒DNA合成具有剂量依赖性抑制作用。BVUrd在HSV-1感染的细胞中直接磷酸化，推测是由病毒编码的胸苷激酶（TK）催化，原因如下：（i）BVUrd不能被感染了TK表达缺陷的HSV-1株的细胞提取物磷酸化；（ii）磷酸化作用被多克隆抗HSV-1抗体抑制。在HSV-1感染的细胞内，BVUrd以BVdUMP（BVdUrd 5'-单磷酸）的形式掺入病毒DNA。这种掺入可能解释了BVUrd的抗病毒作用，这意味着，在被病毒TK初步磷酸化后，BVUrd最有可能在5'-二磷酸水平转化为其2'-脱氧类似物（BVUDP→BVdUDP）。
