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Modulation of HIV-1 replication by RNA interference

Author

Listed:
  • 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)

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.

Suggested Citation

  • Jean-Marc Jacque & Karine Triques & Mario Stevenson, 2002. "Modulation of HIV-1 replication by RNA interference," Nature, Nature, vol. 418(6896), pages 435-438, July.
    • Handle: RePEc:nat:nature:v:418:y:2002:i:6896:d:10.1038_nature00896
    DOI: 10.1038/nature00896
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