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 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.
Jacque
Jean-Marc
JM
Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Worcester, Massachusetts 01605, USA.
Triques
Karine
K
Stevenson
Mario
M
D002460:Cell Line; D016679:Genome, Viral; D054303:HIV Reverse Transcriptase / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology / Q000235:genetics / Q000254:growth & development*; D006801:Humans; D008214:Lymphocytes / Q000821:virology; D010957:Plasmids / Q000235:genetics; D020871:RNA Stability / Q000187:drug effects; D012330:RNA, Double-Stranded / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D034741:RNA, Small Interfering; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013698:Templates, Genetic; D014779:Virus Replication / Q000187:drug effects; D019892:eIF-2 Kinase / Q000378:metabolism
D012330:RNA, Double-Stranded; D034741:RNA, Small Interfering; D022661:RNA, Untranslated; D012367:RNA, Viral; D019892:eIF-2 Kinase; D054303:HIV Reverse Transcriptase