Differential antiviral activities and intracellular metabolism of 3'-azido-3'-deoxythymidine and 2',3'-dideoxyinosine in human cells.
Differential antiviral activities and intracellular metabolism of 3'-azido-3'-deoxythymidine and 2',3'-dideoxyinosine in human cells.
复制标题
人体细胞中 3-azido-3-deoxythymidine 和 2,3-dideoxyinosine 的差异抗病毒活性和细胞内代谢。
DOI：
10.1128/aac.38.7.1573
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发表时间：
1994
影响因子：
4.9
通讯作者：
Mathes,LE
中科院分区：
文献类型：
--
作者：
Mukherji,E;Au,JL;Mathes,LE
双脱氧核苷如3'-叠氮-3'-脱氧胸腺嘧啶（AZT）和2',3'-二脱氧肌苷（ddI）可以有效抑制人类免疫缺陷病毒（HIV）在T淋巴样细胞中的复制。有证据表明，艾滋病毒可以感染和复制其他细胞，包括单核细胞和巨噬细胞。本研究比较了ddI和AZT在MOLT4 （T淋巴细胞样细胞，CD4+）、U937（单核细胞样细胞，CD4+）和HT1080（成纤维细胞样细胞，CD4-）三个人类细胞谱系中的抗逆转录病毒活性。猫白血病病毒，一种导致猫免疫缺陷的逆转录病毒，被用来感染细胞。测定了将细胞裂解物中病毒p27抗原滴度降低50% （ic50）所需的药物浓度。数据显示AZT和ddI抑制了所有三种细胞系的病毒复制。AZT在MOLT4、HT1080和U937细胞中的ic50分别为0.02、1.75和2.31微米。ddI的ic50分别为4.31、9.52和43.5微米。这些数据表明，ddI和AZT在不同细胞中的抗病毒活性存在差异，其药物敏感性排序如下：MOLT4 > HT1080 > U937。对[3H]AZT和[3H]ddI细胞内代谢的研究表明，三种细胞系中AZT和ddI的抗逆转录病毒活性与其细胞内三磷酸代谢物的水平相关。
Dideoxynucleosides such as 3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxyinosine (ddI) can effectively inhibit the replication of human immunodeficiency virus (HIV) in T lymphoid cells. There is evidence that HIV can infect and replicate in other cells including monocytoid cells and macrophages. The present study compared the antiretroviral activities of ddI and AZT in three lineages of human cells, i.e., MOLT4 (T lymphocytoid, CD4+), U937 (monocytoid, CD4+), and HT1080 (fibroblastoid, CD4-) cells. Feline leukemia virus, a retrovirus that causes immunodeficiency in cats, was used to infect the cells. The drug concentrations needed to reduce the viral p27 antigen titers in cell lysates by 50% (IC50s) were determined. The data show that AZT and ddI inhibited viral replication in all three cell lines. The IC50s of AZT were 0.02, 1.75, and 2.31 microM in MOLT4, HT1080, and U937 cells, respectively. For ddI, the IC50s were 4.31, 9.52, and 43.5 microM, respectively. These data indicate differential antiviral activities of ddI and AZT in the different cells with the following rank order of drug sensitivity: MOLT4 > HT1080 > U937. A study of the intracellular metabolism of [3H]AZT and [3H]ddI shows that the antiretroviral activities of AZT and ddI in the three cell lines correlated with the levels of their intracellular triphosphate metabolites.