Phosphorothioate oligodeoxycytidine interferes with binding of HIV-1 gp120 to CD4.

Phosphorothioate oligodeoxycytidine interferes with binding of HIV-1 gp120 to CD4.
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硫代磷酸寡脱氧胞苷干扰 HIV-1 gp120 与 CD4 的结合。

DOI:
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发表时间:
1991
期刊:
Journal of Acquired Immune Deficiency Syndromes
影响因子:
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通讯作者:
Ranajit Pal
Ranajit Pal
中科院分区:
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文献类型:
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作者:
Cy A. Stein;L. Neckers;B. Nair;S. Mumbauer;George M. Hoke;Ranajit Pal

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除了它们作为基因表达的序列特异性抑制剂的特性之外,序列非特异性硫代磷酸寡脱氧核苷酸已被证明可以防止HIV-1的细胞病变效应。虽然这些化合物在体外是HIV-1逆转录酶的有效抑制剂,但不能肯定它们仅以这种方式发挥其细胞保护作用。HIV-1病毒粒子与细胞的初始结合涉及病毒包膜蛋白gp 120与CD 4的相互作用。在这份报告中,我们描述了流式细胞术的数据和固相ELISA检测,记录的能力,硫代脱氧胞苷28聚体干扰这种相互作用的竞争与gp 120结合CD 4。这种相互作用的生物学重要性通过硫代磷酸寡脱氧胞苷抑制HIV-1诱导的细胞融合导致的合胞体形成的事实证明。这些数据表明,硫代磷酸寡脱氧核苷酸可能发挥其细胞保护作用,也许至少部分,通过干扰HIV-1的结合的靶细胞。
In addition to their properties as sequence-specific inhibitors of gene expression, sequence nonspecific phosphorothioate oligodeoxynucleotides have been shown to protect against the cytopathic effects of HIV-1. Although these compounds are effective inhibitors of HIV-1 reverse transcriptase in vitro, it is not certain that they exert their cytoprotective effect only in this manner. Initial binding of the HIV-1 virion to cells involves the interaction of the viral envelope protein gp120 with CD4. In this report, we describe flow cytometric data and a solid-phase ELISA assay that document the ability of a phosphorothioate deoxycytidine 28-mer to interfere with this interaction by competing with gp120 binding to CD4. The biological importance of this interaction is demonstrated by the fact that phosphorothioate oligodeoxycytidine inhibits syncytium formation resulting from HIV-1-induced cell fusion. These data suggest that phosphorothioate oligodeoxynucleotides may exert their cytoprotective effects, perhaps at least in part, by interfering with the binding of HIV-1 to the target cells.