Nishiyama Y, Fujioka H, Tsurumi T, Yamamoto N, Maeno K, Yoshida S, Shimokata K
J Gen Virol. 1987 Mar;68 ( Pt 3):913-8. doi: 10.1099/0022-1317-68-3-913.
It has been recently shown that VP-16-213, a semi-synthetic derivative of podophyllotoxin, inhibits the function of mammalian DNA topoisomerase II. In the present study, we examined the effects of VP-16-213 on the replication of herpes simplex virus type 2 (HSV-2). The compound did not inhibit the synthesis of early viral polypeptides at concentrations at which viral DNA synthesis was strongly suppressed, but induced double-strand breaks in newly synthesized HSV DNA. Electron microscopic examination of treated cells revealed the presence of a number of capsids with empty or partial cores. The level of topoisomerase II activity remained unaltered after infection, and all attempts to isolate VP-16-213-resistant mutants of HSV-2 have failed in spite of extensive efforts. It is suggested therefore that the mode of action of VP-16-213 may be inhibition of viral DNA synthesis by impairing the function of host cell topoisomerase II.
最近研究表明，鬼臼毒素的半合成衍生物VP - 16 - 213可抑制哺乳动物DNA拓扑异构酶II的功能。在本研究中，我们检测了VP - 16 - 213对2型单纯疱疹病毒（HSV - 2）复制的影响。该化合物在强烈抑制病毒DNA合成的浓度下，并不抑制早期病毒多肽的合成，但会在新合成的HSV DNA中诱导双链断裂。对处理过的细胞进行电子显微镜检查发现存在许多衣壳核心为空或部分为空的情况。感染后拓扑异构酶II的活性水平保持不变，尽管进行了大量努力，但所有分离HSV - 2的VP - 16 - 213抗性突变体的尝试均告失败。因此，提示VP - 16 - 213的作用方式可能是通过损害宿主细胞拓扑异构酶II的功能来抑制病毒DNA合成。
