ACYCLOVIR INHIBITION OF EPSTEIN-BARR VIRUS-REPLICATION
ACYCLOVIR INHIBITION OF EPSTEIN-BARR VIRUS-REPLICATION
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DOI：
10.1073/pnas.77.9.5163
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发表时间：
1980-01-01
期刊：
影响因子：
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通讯作者：
PAGANO, JS
中科院分区：
文献类型：
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作者：
DATTA, AK;COLBY, BM;PAGANO, JS
阿昔洛韦[9-(2-羟乙氧甲基)鸟嘌呤]三磷酸对EB病毒(EBV)相关DNA聚合酶(DNA核苷酸转移酶；EC 2.7.7.7)的抑制程度大于对宿主α的抑制。和测试版。DNA聚合酶。该化合物对病毒聚合酶的亲和力比对α-聚合酶的亲和力高100倍。抑制的程度取决于模板-底物的碱基组成。这种抑制可以通过增加脱氧鸟苷三磷酸的浓度来防止。在抑制物存在的情况下，EBV相关的DNA聚合酶反应虽然受到抑制，但在很长一段时间内以线性速度进行。相反，大肠杆菌DNA聚合酶I在DNA链终止子2‘’，3‘’-二脱氧胸苷5‘’-三磷酸存在下的反应在初始线性后趋于平稳。将三磷酸阿昔洛韦与DNA和酶预先孵育并不能增加其抑制活性。病毒产生细胞株P3HR-1[人Burkitt‘’S淋巴瘤]长期暴露于阿昔洛韦后，病毒基因组数量和病毒衣壳抗原持续减少，在无药物培养时，病毒基因组数量恢复到对照水平。结果表明，竞争机制是阿昔洛韦抑制EB病毒复制的主要机制。
Acyclovir [9-(2-hydroxyethoxymethyl)guanine] triphosphate inhibits Epstein-Barr virus (EBV)-associated DNA polymerase (DNA nucleotidyltransferase; EC 2.7.7.7) to a greater extent than it inhibits host .alpha. and .beta. DNA polymerases. The affinity of the compound for viral polymerase is 100-fold higher than for .alpha.-polymerase. The extent of inhibition is dependent upon the base composition of the template-primer. The inhibition is prevented by increasing concentrations of deoxyguanosine triphosphate. The EBV-associated DNA polymerase reaction in the presence of the inhibitor, although depressed, proceeds at a linear rate over a long period of time. In contrast, the reaction of Escherichia coli DNA polymerase I in the presence of 2'',3''-dideoxythymidine 5''-triphosphate, a DNA chain terminator, levels off after initial linearity. Preincubation of acyclovir triphosphate with DNA and enzyme does not increase its inhibitory activity. The virus-producing cell line P3HR-1 [human Burkitt''s lymphoma] consistently shows reduced viral genome numbers and viral capsid antigen on prolonged exposure to acyclovir. The number of EBV genomes returns to the control level when the cells are grown in drug-free medium. The results suggest that a competitive mechanism is the major mode of acyclovir inhibition of EBV replication.