5-AZACYTIDINE AND 5-AZADEOXYCYTIDINE INHIBIT HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REPLICATION INVITRO
5-AZACYTIDINE AND 5-AZADEOXYCYTIDINE INHIBIT HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REPLICATION INVITRO
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DOI：
10.1128/aac.34.2.206
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发表时间：
1990-02-01
影响因子：
4.9
通讯作者：
THIBODEAU, L
中科院分区：
文献类型：
--
作者：
BOUCHARD, J;WALKER, MC;THIBODEAU, L
影响人类免疫缺陷病毒（HIV）前病毒整合、稳定或诱导的化学药物在治疗获得性免疫缺陷综合征中具有相当大的价值。胞嘧啶的两种核苷类似物，5-氮杂胞苷和5-氮脱氧胞苷，由于它们能够影响它们所掺入的核酸的稳定性和甲基化模式，因此似乎具有这样的价值，测试了它们在体外抑制人CEM T细胞中HIV 1型（HIV-1）复制的能力。5-根据降低的病毒抗原表达和降低的上清液逆转录酶活性的标准，氮脱氧胞苷（1 μ M）几乎完全抑制CEM细胞中的HIV复制，对处理的细胞几乎没有毒性。5-氮杂胞苷（1 μ M）也抑制HIV复制，但不太有效。当在CEM细胞感染HIV-1后2小时或更长时间加入时，两种5-氮杂胞嘧啶衍生物的效果都不如在感染时加入时的效果。即使暴露于5-氮脱氧胞苷2小时也足以抑制HIV复制。尽管长时间暴露于1 μ M浓度的任一类似物将导致显著的细胞毒性，但短时间暴露于相同剂量的药物抑制HIV复制但对细胞无毒的事实暗示细胞毒性本身不是类似物抗病毒作用的重要机制。
Chemotherapeutic agents which affect the integration, stability, or inducibility of the human immunodeficiency virus (HIV) provirus would have considerable value in treating acquired immunodeficiency syndrome. Two nucleoside analogs of cytosine, 5-azacytidine and 5-azadeoxycytidine, which seem to have such value because of their capabilities to affect both the stability and the methylation patterns of the nucleic acids into which they are incorporated, were tested for their ability to inhibit the replication of HIV type 1 (HIV-1) in human CEM T cells in vitro. 5-Azadeoxycytidine (1 .mu.M) almost completely inhibited HIV replication in CEM cells, by the criteria of reduced viral antigen expression and decreased supernatant reverse transcriptase activity, with little toxicity for the treated cells. 5-Azacytidine (1 .mu.M) also inhibited HIV replication, but less effectively. When added 2 or more h after CEM cells were infected with HIV-1, both 5-azacytosine derivatives were less effective than they were when added at the time of infection. Even 2 h of exposure to 5-azadeoxycytidine was sufficient for inhibition of HIV replication. Although long exposure to either analog at concentrations of 1 .mu.M would result in pronounced cellular cytotoxicity, the fact that short exposures to the same dose of drug inhibit HIV replication but are not toxic for the cells implies that cellular toxicity itself is not an important mechanism of the antiviral action of the analogs.