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Journal of Virology, November 2003, p. 11964-11972, Vol. 77, No. 22
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.22.11964-11972.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Inhibition of Human Immunodeficiency Virus Type 1 Replication in Primary Macrophages by Using Tat- or CCR5-Specific Small Interfering RNAs Expressed from a Lentivirus Vector

Ming-Ta M. Lee,1 Glen A. Coburn,1 Myra O. McClure,2 and Bryan R. Cullen1*

Howard Hughes Medical Institute and Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710,1 Jefferiss Research Trust Laboratories, Wright-Fleming Institute, Imperial College School of Medicine at St. Mary's, London W2 1PG, United Kingdom2

Received 27 May 2003/ Accepted 28 July 2003

Although several groups have demonstrated that RNA interference, induced by transfection of small interfering RNA (siRNA) duplexes, can protect cells against a viral challenge in culture, this protection is transient. Here, we describe lentivirus expression vectors that can stably express siRNAs at levels sufficient to block virus replication. We have used these vectors to stably express siRNAs specific for the essential human immunodeficiency virus type 1 (HIV-1) Tat transcription factor or specific for a cellular coreceptor, CCR5, that is required for infection by the majority of primary HIV-1 isolates. These lentivirus vectors are shown to protect cells, including primary macrophages, against HIV-1 infection in culture by inducing selective degradation of their target mRNA species. These data suggest that it should be possible to block the expression of specific viral or cellular genes in vivo by using viral vectors to stably express the appropriate siRNAs.

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

Journal of Virology, November 2003, p. 11964-11972, Vol. 77, No. 22
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.22.11964-11972.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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