Pagano J S, Datta A K
Am J Med. 1982 Jul 20;73(1A):18-26. doi: 10.1016/0002-9343(82)90057-2.
Acyclovir [9-(2-hydroxyethoxymethyl)guanine] inhibits Epstein-Barr virus (EBV) replication in lymphoblastoid cells at concentrations nontoxic to cellular growth. The mode of action of the drug against EBV differs from the mechanism described in herpes simplex virus systems. Due to the absence of virus-specified thymidine kinase, the drug is poorly phosphorylated in EBV-infected cells. The extent of monophosphorylation is similar both in mock-infected and EBV-infected cells. Despite weak phosphorylation of the drug, the replication of linear EBV DNA is inhibited due to exquisite sensitivity of the viral DNA polymerase. Activation of acyclovir does not require phosphorylation by virus-specified thymidine kinase, inhibition of different herpes-group viruses depends on three variable factors: degree of phosphorylation, cellular metabolism of the drug, and degree of sensitivity of the viral polymerase. Interaction of acyclovir-triphosphate with EBV DNA polymerase is reversible. Cells infected with EBV and treated with acyclovir resume virus replication following removal of the drug even after long exposure. Acyclovir inhibits replication of linear genomes and stops production of virus, but has no effect on latent cellular infection. These results lead us to predict that acyclovir will suppress, but not cure, EBV infection.
阿昔洛韦[9 -（2 - 羟乙氧甲基）鸟嘌呤]在对细胞生长无毒的浓度下可抑制淋巴母细胞中爱泼斯坦 - 巴尔病毒（EBV）的复制。该药物针对EBV的作用模式不同于单纯疱疹病毒系统中所描述的机制。由于缺乏病毒特异性胸苷激酶，该药物在EBV感染的细胞中磷酸化程度很低。在 mock 感染细胞和EBV感染细胞中，单磷酸化的程度相似。尽管该药物磷酸化程度较弱，但由于病毒DNA聚合酶的高度敏感性，线性EBV DNA的复制仍受到抑制。阿昔洛韦的激活不需要病毒特异性胸苷激酶的磷酸化，对不同疱疹病毒组病毒的抑制取决于三个可变因素：磷酸化程度、药物的细胞代谢以及病毒聚合酶的敏感程度。阿昔洛韦三磷酸与EBV DNA聚合酶的相互作用是可逆的。用阿昔洛韦处理过的EBV感染细胞，即使在长时间暴露后，去除药物后仍会恢复病毒复制。阿昔洛韦抑制线性基因组的复制并停止病毒产生，但对细胞潜伏感染没有影响。这些结果使我们预测，阿昔洛韦将抑制但不能治愈EBV感染。
