Modulation of HIV-1 replication by RNA interference
Modulation of HIV-1 replication by RNA interference
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DOI：
10.1038/nature00896
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发表时间：
2002-07-25
期刊：
影响因子：
64.8
通讯作者：
Stevenson, M
中科院分区：
文献类型：
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作者：
Jacque, JM;Triques, K;Stevenson, M
RNA干扰(RNAi)是双链RNA(DsRNA)在动植物细胞中引导信使RNA序列特异性降解的过程(1，2)。在哺乳动物细胞中，小干扰RNA(SiRNA)的21个核苷酸双链可以触发RNAi(3)。在这里，我们描述了针对HIV-1基因组不同区域的siRNA对HIV-1在人类细胞系和初级淋巴细胞中复制的早期和晚期的抑制作用。我们证明了合成的siRNA双链或来自质粒的siRNAs通过特异性地降解基因组HIV-1RNA来抑制HIV-1感染，从而防止病毒互补DNA中间体的形成。这些结果证明了RNAi在调节HIV复制周期方面的有效性，并提供了证据，表明基因组HIV-1RNA存在于核蛋白逆转录复合体中，易于由siRNA介导的降解。
RNA interference (RNAi) is the process by which double-stranded RNA (dsRNA) directs sequence-specific degradation of messenger RNA in animal and plant cells(1,2). In mammalian cells, RNAi can be triggered by 21-nucleotide duplexes of small interfering RNA (siRNA)(3). Here we describe inhibition of early and late steps of HIV-1 replication in human cell lines and primary lymphocytes by siRNAs targeted to various regions of the HIV-1 genome. We demonstrate that synthetic siRNA duplexes or plasmid-derived siRNAs inhibit HIV-1 infection by specifically degrading genomic HIV-1 RNA, thereby preventing formation of viral complementary-DNA intermediates. These results demonstrate the utility of RNAi for modulating the HIV replication cycle and provide evidence that genomic HIV-1 RNA, as it exists within a nucleoprotein reverse-transcription complex, is amenable to siRNA-mediated degradation.