Smith M S, Brian E L, Pagano J S
Lineberger Cancer Research Center, University of North Carolina, Chapel Hill 27514.
J Virol. 1987 Dec;61(12):3769-73. doi: 10.1128/JVI.61.12.3769-3773.1987.
The new antiviral agent, azidothymidine (AZT; BW A509U), is currently the only successful drug in use for patients with acquired immunodeficiency syndrome. The effect of this thymidine analog, 3'-azido-3'-deoxythymidine, on the replication of the lymphadenopathy-associated virus strain of the human immunodeficiency virus was evaluated by using susceptible H9 and Jurkat cells. Cells were pretreated with concentrations of drug ranging from 0.5 to 100 microM, infected, and maintained in medium containing drug. Virus production was assayed by reverse transcriptase assays, and virus-specific DNA was analyzed by Southern blots probed with cloned human immunodeficiency virus sequences. At 4 to 8 days postinfection, infected cells without drug reached a peak of reverse transcriptase activity that was sustained. Increasing concentrations of AZT caused increasing delays in virus production; however, replicate cultures at nontoxic levels of the drug (up to 25 microM) eventually produced as much virus as did non-drug-treated infected cells, despite the continued presence of the drug. Levels of intracellular, unintegrated, virus-specific DNA paralleled reverse transcriptase levels. Virus-caused cytopathic effect was likewise delayed in drug-treated cultures. Virus recovered from H9 cultures after 25 microM AZT treatment did not appear resistant to AZT.
新型抗病毒药物叠氮胸苷（AZT；BW A509U）是目前用于获得性免疫缺陷综合征患者的唯一成功药物。通过使用敏感的H9和Jurkat细胞，评估了这种胸苷类似物3'-叠氮-3'-脱氧胸苷对人类免疫缺陷病毒淋巴结病相关病毒株复制的影响。细胞用浓度范围为0.5至100微摩尔的药物预处理，感染后，在含有药物的培养基中培养。通过逆转录酶测定法检测病毒产生，并通过用克隆的人类免疫缺陷病毒序列探测的Southern印迹分析病毒特异性DNA。在感染后4至8天，未用药物处理的感染细胞达到持续的逆转录酶活性峰值。AZT浓度增加导致病毒产生的延迟增加；然而，在药物无毒水平（高达25微摩尔）下的重复培养物最终产生的病毒量与未用药物处理的感染细胞相同，尽管药物持续存在。细胞内未整合的病毒特异性DNA水平与逆转录酶水平平行。在药物处理的培养物中，病毒引起的细胞病变效应同样延迟。在25微摩尔AZT处理后从H9培养物中回收的病毒似乎对AZT没有抗性。
