Potent and specific inhibition of human immunodeficiency virus type 1 replication by RNA interference.
Synthetic small interfering RNAs (siRNAs) have been shown to induce the degradation of specific mRNA targets in human cells by inducing RNA interference (RNAi). Here, we demonstrate that siRNA duplexes targeted against the essential Tat and Rev regulatory proteins encoded by human immunodeficiency virus type 1 (HIV-1) can specifically block Tat and Rev expression and function. More importantly, we show that these same siRNAs can effectively inhibit HIV-1 gene expression and replication in cell cultures, including those of human T-cell lines and primary lymphocytes. These observations demonstrate that RNAi can effectively block virus replication in human cells and raise the possibility that RNAi could provide an important innate protective response, particularly against viruses that express double-stranded RNAs as part of their replication cycle.
Coburn
Glen A
GA
Howard Hughes Medical Institute and Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Cullen
Bryan R
BR
D002460:Cell Line; D002478:Cells, Cultured; D015967:Gene Expression Regulation, Viral; D015694:Gene Products, rev / Q000235:genetics / Q000378:metabolism; D015696:Gene Products, tat / Q000235:genetics / Q000378:metabolism; D015757:Genes, rev; D015756:Genes, tat; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear / Q000821:virology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering; D022661:RNA, Untranslated / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000821:virology; D014779:Virus Replication / Q000187:drug effects* / Q000502:physiology; D054321:rev Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus
D015694:Gene Products, rev; D015696:Gene Products, tat; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D022661:RNA, Untranslated; D054321:rev Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus