Modulation of HIV-1 replication by RNA interference


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.

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Figure 1: Small interfering RNAs inhibit late events in HIV replication by promoting degradation of HIV-1 RNA.
Figure 2: Small interfering RNAs block early events in HIV replication by promoting degradation of genomic HIV RNA.
Figure 3: Inhibition of HIV replication by siRNAs derived from plasmid DNA templates.


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We thank A. Mann for research support, C. Mello and P. Zamore for discussions, B. Mellor for preparation of the figures, and T. Pinkos for manuscript preparation. We also acknowledge assay support provided by the University of Massachusetts Center for AIDS Research. HIVYU-2 was obtained through the AIDS Research and Reference Reagent Program, Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), from B. Hahn and G. Shaw. This study was supported by grants from the NIH and the Jenner Foundation to M.S.

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Correspondence to Mario Stevenson.

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Jacque, J., Triques, K. & Stevenson, M. Modulation of HIV-1 replication by RNA interference. Nature 418, 435–438 (2002).

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