Colby B M, Furman P A, Shaw J E, Elion G B, Pagano J S
J Virol. 1981 May;38(2):606-11. doi: 10.1128/JVI.38.2.606-611.1981.
The extent of phosphorylation of 9-(2-hydroxyethoxymethyl)guanine (acyclovir [ACV]) in fresh peripheral leukocytes, in Epstein-Barr virus (EBV)-infected lymphoblastoid cell lines, and in herpes simplex virus type 1-infected lymphoblastoid (P3HR-1) and monkey kidney (Vero) cells was determined by high-pressure liquid chromatography, Mono-, di-, and triphosphorylated derivatives of [8-14C]ACV were detected at low levels at various times after superinfection of Raji cells with EBV. The extent of phosphorylation appeared to be related to the concentration of ACV in the medium. Small amounts of ACV mono-, di-, and triphosphates were formed in fresh peripheral leukocyte preparations from EBV- seropositive and -seronegative donors. Comparable ACV monophosphate levels were detected in EBV-negative BJAB and the EBV-positive BJAB/GC cell lines; however, no di- or triphosphate derivatives were detected. Comparable ACV-monophosphate levels were detected in both P3HR-1 and HSV-infected P3HR-1 cell lines; however, larger amounts of ACV di- and triphosphorylated derivatives were detected in the HSV-infected P3HR-1 cells. ACV was converted to the triphosphate to a greater extent in HSV-infected Vero cells than in mock-infected Vero cells or in HSV-infected P3HR-1 cells. ACV or its phosphorylated derivatives were converted to guanine nucleotides to a greater extent in lymphoblastoid cells than in fibroblasts (Vero). In conclusion, neither the productive replication of EBV nor the presence of latent viral DNA is required for ACV monophosphate formation in B lymphoblastoid cells. ACV triphosphate, however, was detected only in cells infected productively with EBV.
通过高压液相色谱法测定了新鲜外周血白细胞、爱泼斯坦-巴尔病毒（EBV）感染的淋巴母细胞系、单纯疱疹病毒1型感染的淋巴母细胞（P3HR-1）和猴肾（Vero）细胞中9-(2-羟乙氧甲基)鸟嘌呤（阿昔洛韦[ACV]）的磷酸化程度。用EBV超感染Raji细胞后不同时间，低水平检测到了[8-14C]ACV的单磷酸、二磷酸和三磷酸衍生物。磷酸化程度似乎与培养基中ACV的浓度有关。EBV血清阳性和血清阴性供体的新鲜外周血白细胞制剂中形成了少量的ACV单磷酸、二磷酸和三磷酸。在EBV阴性的BJAB和EBV阳性的BJAB/GC细胞系中检测到了相当的ACV单磷酸水平；然而，未检测到二磷酸或三磷酸衍生物。在P3HR-1和单纯疱疹病毒感染的P3HR-1细胞系中检测到了相当的ACV单磷酸水平；然而，在单纯疱疹病毒感染的P3HR-1细胞中检测到了更多的ACV二磷酸和三磷酸化衍生物。与未感染的Vero细胞或单纯疱疹病毒感染的P3HR-1细胞相比，单纯疱疹病毒感染的Vero细胞中ACV转化为三磷酸的程度更高。与成纤维细胞（Vero）相比，ACV或其磷酸化衍生物在淋巴母细胞中转化为鸟嘌呤核苷酸的程度更高。总之，B淋巴母细胞中ACV单磷酸的形成既不需要EBV的有效复制，也不需要潜伏病毒DNA的存在。然而，仅在被EBV有效感染的细胞中检测到了ACV三磷酸。
