Potent and specific inhibition of human immunodeficiency virus type 1 replication by RNA interference

Potent and specific inhibition of human immunodeficiency virus type 1 replication by RNA interference
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DOI:
10.1128/jvi.76.18.9225-9231.2002
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发表时间:
2002-09-01
影响因子:
5.4
通讯作者:
Cullen, BR
Cullen, BR
中科院分区:
医学2区
文献类型:
--
作者:
Coburn, GA;Cullen, BR

文献摘要

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相似文献

合成的小干扰RNA (sirna)已被证明可以通过诱导RNA干扰(RNAi)诱导人类细胞中特定mRNA靶标的降解。在这里,我们证明了针对人类免疫缺陷病毒1型(HIV-1)编码的必需Tat和Rev调节蛋白的siRNA双链可以特异性地阻断Tat和Rev的表达和功能。更重要的是,我们发现这些相同的sirna可以有效地抑制细胞培养中HIV-1基因的表达和复制,包括人类t细胞系和原代淋巴细胞。这些观察结果表明,RNAi可以有效地阻断病毒在人类细胞中的复制,并提出了RNAi可能提供重要的先天保护反应的可能性,特别是针对表达双链rna作为其复制周期一部分的病毒。
Synthetic small interfering RNAs (siRNAs) have been shown to induce the degradation of specific mRNA targets in human cells by inducing RNA interference (RNAi). Here, we demonstrate that siRNA duplexes targeted against the essential Tat and Rev regulatory proteins encoded by human immunodeficiency virus type 1 (HIV-1) can specifically block Tat and Rev expression and function. More importantly, we show that these same siRNAs can effectively inhibit HIV-1 gene expression and replication in cell cultures, including those of human T-cell lines and primary lymphocytes. These observations demonstrate that RNAi can effectively block virus replication in human cells and raise the possibility that RNAi could provide an important innate protective response, particularly against viruses that express double-stranded RNAs as part of their replication cycle.