Langelier Y, Buttin G
J Gen Virol. 1981 Nov;57(Pt 1):21-31. doi: 10.1099/0022-1317-57-1-21.
Ribonucleotide reductase is an essential enzyme in mammalian DNA replication. In quiescent BHK-21/C13 cells exhibiting a low level of ribonucleotide reductase activity, infection with herpes simplex virus (HSV) resulted in the early induction of an altered ribonucleotide reductase. The extent of the induction was dependent upon the m.o.i. and could be diminished or prevented by u.v. treatment of the viral stock, or by inhibitors of mRNA synthesis or protein synthesis. The induction followed the same course of synthesis as viral thymidine kinase and DNA polymerase, and could thus be classified with them as a beta polypeptide. These results suggested that the new activity was produced as a consequence of the virus genome expression. Comparisons of the properties of ribonucleotide reductase extracted from exponentially growing BHK-21/C13 cells showed that the HSV-induced enzyme differed from the cellular isozyme by its insensitivity to inhibition by dTTP, dATP or araATP and its resistance to high salt concentrations. On the other hand, the virus-induced enzyme and the cellular isozyme exhibited a similar sensitivity to hydroxyurea. Therefore, the reported inhibition of HSV DNA replication by hydroxyurea could be the result of inhibition of both HSV-induced and cellular reductase activities.
核糖核苷酸还原酶是哺乳动物DNA复制中的一种关键酶。在静止的BHK - 21/C13细胞中，核糖核苷酸还原酶活性水平较低，感染单纯疱疹病毒（HSV）会导致一种改变的核糖核苷酸还原酶的早期诱导。诱导程度取决于感染复数（m.o.i.），并且可以通过对病毒储备液进行紫外线处理，或通过mRNA合成抑制剂或蛋白质合成抑制剂来减弱或阻止。这种诱导与病毒胸苷激酶和DNA聚合酶遵循相同的合成过程，因此可以与它们一起归类为β多肽。这些结果表明，新的活性是病毒基因组表达的结果。对从指数生长的BHK - 21/C13细胞中提取的核糖核苷酸还原酶特性的比较表明，HSV诱导的酶与细胞同工酶不同，它对dTTP、dATP或araATP的抑制不敏感，并且对高盐浓度具有抗性。另一方面，病毒诱导的酶和细胞同工酶对羟基脲表现出相似的敏感性。因此，报道的羟基脲对HSV DNA复制的抑制可能是抑制HSV诱导的和细胞还原酶活性的结果。
