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2',3'-二脱氢-2',3'-二脱氧核苷对人类免疫缺陷病毒的感染性、细胞病变效应及复制的抑制作用

Inhibitory effect of 2',3'-didehydro-2',3'-dideoxynucleosides on infectivity, cytopathic effects, and replication of human immunodeficiency virus.

作者信息

Hamamoto Y, Nakashima H, Matsui T, Matsuda A, Ueda T, Yamamoto N

出版信息

Antimicrob Agents Chemother. 1987 Jun;31(6):907-10. doi: 10.1128/AAC.31.6.907.

Abstract

It is generally accepted that human immunodeficiency virus (HIV) is the etiologic agent of the acquired immunodeficiency syndrome and related diseases. In this report, we demonstrate the antiviral effect of nucleoside analogs 2',3'-didehydro-2',3'-dideoxythymidine (DHT) and 2',3'-didehydro-2',3'-dideoxycytidine (DHC) by using human T-cell lymphotropic virus type I-carrying MT-4 cells, which are extremely susceptible to HIV infection. These agents efficiently inhibited the cytopathic effects and expression of HIV-specific antigens in MT-4 cells after infection of the virus. Both DHT and DHC also strongly blocked viral replication as determined by our quantitative bioassay system using a plaque-forming assay. These antiviral effects were obtained at concentrations at which the drugs produced little or no toxicity and were comparable to those with 3'-azido-3'-deoxythymidine and 2',3'-dideoxynucleosides. These findings warrant further investigation of the use of DHT and DHC for the treatment of the acquired immunodeficiency syndrome and related diseases.

摘要

人们普遍认为,人类免疫缺陷病毒(HIV)是获得性免疫缺陷综合征及相关疾病的病原体。在本报告中,我们使用携带I型人类嗜T细胞病毒的MT-4细胞(该细胞对HIV感染极为敏感),证明了核苷类似物2',3'-二脱氢-2',3'-二脱氧胸苷(DHT)和2',3'-二脱氢-2',3'-二脱氧胞苷(DHC)的抗病毒作用。在病毒感染MT-4细胞后,这些药物有效抑制了细胞病变效应以及HIV特异性抗原的表达。通过我们使用噬斑形成试验的定量生物测定系统确定,DHT和DHC均强烈阻断了病毒复制。这些抗病毒作用是在药物产生很少或没有毒性的浓度下获得的,并且与3'-叠氮基-3'-脱氧胸苷和2',3'-二脱氧核苷的作用相当。这些发现值得进一步研究DHT和DHC在治疗获得性免疫缺陷综合征及相关疾病中的应用。

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