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Journal of Virology, September 2002, p. 9225-9231, Vol. 76, No. 18
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.18.9225-9231.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Potent and Specific Inhibition of Human Immunodeficiency Virus Type 1 Replication by RNA Interference

Glen A. Coburn and Bryan R. Cullen*

Howard Hughes Medical Institute and Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710

Received 5 April 2002/ Accepted 10 June 2002

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.

* Corresponding author. Mailing address: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Box 3025, Durham, NC 27710. Phone: (919) 684-3369. Fax: (919) 681-8979. E-mail: culle002{at}mc.duke.edu.

Journal of Virology, September 2002, p. 9225-9231, Vol. 76, No. 18
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.18.9225-9231.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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