MODE OF ACTION OF ACYCLOVIR TRIPHOSPHATE ON HERPESVIRAL AND CELLULAR DNA-POLYMERASES
MODE OF ACTION OF ACYCLOVIR TRIPHOSPHATE ON HERPESVIRAL AND CELLULAR DNA-POLYMERASES
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DOI：
10.1016/0166-3542(82)90014-6
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发表时间：
1982-01-01
影响因子：
7.6
通讯作者：
SEHGAL, RK
中科院分区：
文献类型：
--
作者：
ALLAUDEEN, HS;DESCAMPS, J;SEHGAL, RK
无环鸟苷5 " -三磷酸（ACV）对2种人类疱疹病毒-单纯疱疹病毒1型（HSV-1）和eb病毒（EBV） DNA聚合酶及人类细胞DNA聚合酶的影响。和度量。已经检查过了。在测试的酶中，HSV-1 DNA聚合酶对三磷酸无环鸟苷（ACVTP）的抑制最为敏感。eb病毒DNA聚合酶和DNA聚合酶。不那么敏感。ACVTP抑制与dGTP具有竞争性，Ki值分别为0.03、0.15、9.8和11.9 .mu。M代表HSV-1 DNA聚合酶，DNA聚合酶。， eb病毒DNA聚合酶和DNA聚合酶。,分别。取代合成引物模板（dG.apprx）。15 .cntdot。（dC）n对活化DNA模板没有改变抑制模式。在一个时间过程实验中，添加ACVTP代替dGTP并没有增加DNA的合成，它似乎在HSV-1 DNA聚合酶或DNA聚合酶催化的DNA复制中起链终止器的作用。虽然EBV DNA聚合酶对ACVTP抑制不太敏感，但核苷类似物本身对[人淋巴母细胞]P3HR1细胞系产生EBV具有抑制作用，这是通过表达病毒衣壳抗原（VCA）的细胞百分比的减少来确定的。第4天ACV分别为10和25亩。g/ml分别使细胞生长减少10%和32%，使vca阳性细胞生长减少80%和84%。显然，ACVTP对EBV DNA聚合酶活性的抑制可能不是ACV抑制EBV复制的主要机制。
The effect of 5''-triphosphate of acyclovir (ACV) on DNA polymerases of 2 human herpesviruses, herpes simplex virus type 1 (HSV-1) and Epstein-Barr virus (EBV) as well as human cellular DNA polymerases .alpha. and .beta. has been examined. Of the enzymes tested, HSV-1 DNA polymerase was the most sensitive to inhibition by acyclovir triphosphate (ACVTP). The EBV DNA polymerase and DNA polymerase .beta. were less sensitive. ACVTP inhibition was competitive with dGTP with Ki values of 0.03, 0.15, 9.8 and 11.9 .mu.M for HSV-1 DNA polymerase, DNA polymerase .alpha., EBV DNA polymerase and DNA polymerase .beta., respectively. Substituting a synthetic primer template (dG.apprx. 15 .cntdot. (dC)n for activated DNA template did not alter the pattern of inhibition. In a time course experiment, addition of ACVTP instead of dGTP did not increase DNA synthesis and it appeared to act as a chain terminator in DNA replication catalyzed by either HSV-1 DNA polymerase or DNA polymerase .alpha.. Although EBV DNA polymerase was less sensitive to ACVTP inhibition, the nucleoside analog itself was inhibitory to EBV production by [human lymphoblastoid] P3HR1 cell line as determined by a reduction in the percentage of cells expressing virus capsid antigen (VCA). On day 4, ACV at 10 and 25 .mu.g/ml reduced the cell growth by 10% and 32%, respectively, while it reduced the VCA-positive cells by 80% and 84%, respectively. Evidently, inhibition of EBV DNA polymerase activity by ACVTP may not be the primary mechanism responsible for ACV inhibition of EBV replication.