1. Modulation of HIV-1 replication by RNA interference
- Author
-
Jean-Marc Jacque, Karine Triques, and Mario Stevenson
- Subjects
Small interfering RNA ,RNA, Untranslated ,RNA Stability ,Trans-acting siRNA ,Genome, Viral ,Biology ,Virus Replication ,Article ,Cell Line ,eIF-2 Kinase ,DNA-directed RNA interference ,RNA interference ,Humans ,Lymphocytes ,RNA, Small Interfering ,RNA, Double-Stranded ,Gene knockdown ,Multidisciplinary ,Reverse Transcriptase Polymerase Chain Reaction ,RNA ,Templates, Genetic ,Virology ,Reverse transcriptase ,HIV Reverse Transcriptase ,Viral replication ,HIV-1 ,RNA, Viral ,Plasmids - Abstract
RNA interference (RNAi) is the process by which double-stranded RNA (dsRNA) directs sequence-specific degradation of messenger RNA in animal and plant cells(1,2). 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.
- Published
- 2002