siRNA-directed inhibition of HIV-1 infection

A Corrigendum to this article was published on 01 November 2003

Abstract

RNA interference silences gene expression through short interfering 21–23-mer double-strand RNA segments that guide mRNA degradation in a sequence-specific fashion. Here we report that siRNAs inhibit virus production by targeting the mRNAs for either the HIV-1 cellular receptor CD4, the viral structural Gag protein or green fluorescence protein substituted for the Nef regulatory protein. siRNAs effectively inhibit pre- and/or post-integration infection events in the HIV-1 life cycle. Thus, siRNAs may have potential for therapeutic intervention in HIV-1 and other viral infections.

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Figure 1: CD4-siRNA inhibits HIV-1 entry and infection in Magi-CCR5 cells.
Figure 2: p24-siRNA inhibits viral replication in HeLa-CD4 cells.
Figure 3: 3Time course of silencing HIV-1 gene expression and inhibition of viral replication in H9 T cells.
Figure 4: siRNA-directed silencing of viral gene expression in HeLa-CD4 cells in established HIV-1 infection.
Figure 5: siRNA-directed silencing of viral gene expression after integration.
Figure 6: Model for pathways of RNA interference for inhibition of productive HIV-1 infection.

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Acknowledgements

We thank V. François-Bongarçon for help and technical assistance; H. Cargill for help with Fig. 6; and J. Doench for helpful discussions and comments. The following reagents were obtained through the AIDS Research and Reference Reagent Program Division of AIDS, NIAID, NIH: HeLaT4+ and T4pMV7 were provided by R. Axel, pR7-GFP was provided by K. Page and M. Feinberg and Magi-CCR5 was provided by J. Overbaugh. This work was supported by grants NIH F32 AI10523 (to C.D.N.), NIH T32-GM07748 (to M.F.M.), NIH AI 35502 (to R.G.C.), NIH AI 45306 (to P.S.) and NIH MERIT grant R37-GM34277, NCI grant PO1-CA42063 and partially by NCI Cancer Center Support (Core) grant P30-CA14051 (to P.A.S.).

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Correspondence to Premlata Shankar or Phillip A. Sharp.

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Novina, C., Murray, M., Dykxhoorn, D. et al. siRNA-directed inhibition of HIV-1 infection. Nat Med 8, 681–686 (2002). https://doi.org/10.1038/nm725

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