Modulation of HIV-1 replication by RNA interference

Jean-Marc Jacque, Karine Triques and Mario Stevenson ()
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Jean-Marc Jacque: Program in Molecular Medicine, University of Massachusetts Medical School
Karine Triques: Program in Molecular Medicine, University of Massachusetts Medical School
Mario Stevenson: Program in Molecular Medicine, University of Massachusetts Medical School

Nature, 2002, vol. 418, issue 6896, 435-438

Abstract: Abstract RNA interference (RNAi) is the process by which double-stranded RNA (dsRNA) directs sequence-specific degradation of messenger RNA in animal and plant cells1,2. 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.

Date: 2002
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DOI: 10.1038/nature00896

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