Modulation of HIV-1 replication by RNA interference

Nature. 2002 Jul 25;418(6896):435-8. doi: 10.1038/nature00896. Epub 2002 Jun 26.


RNA interference (RNAi) is the process by which double-stranded RNA (dsRNA) directs sequence-specific degradation of messenger RNA in animal and plant cells. In mammalian cells, RNAi can be triggered by 21-nucleotide duplexes of small interfering RNA (siRNA). 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Line
  • Genome, Viral
  • HIV Reverse Transcriptase / metabolism
  • HIV-1 / drug effects
  • HIV-1 / enzymology
  • HIV-1 / genetics
  • HIV-1 / growth & development*
  • Humans
  • Lymphocytes / virology
  • Plasmids / genetics
  • RNA Stability / drug effects
  • RNA, Double-Stranded / genetics
  • RNA, Double-Stranded / metabolism
  • RNA, Double-Stranded / pharmacology
  • RNA, Small Interfering
  • RNA, Untranslated / genetics
  • RNA, Untranslated / metabolism*
  • RNA, Untranslated / pharmacology
  • RNA, Viral / genetics
  • RNA, Viral / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Templates, Genetic
  • Virus Replication* / drug effects
  • eIF-2 Kinase / metabolism


  • RNA, Double-Stranded
  • RNA, Small Interfering
  • RNA, Untranslated
  • RNA, Viral
  • eIF-2 Kinase
  • HIV Reverse Transcriptase