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Journal of Virology, June 1999, p. 5191-5195, Vol. 73, No. 6
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Potent Inhibition of Human Immunodeficiency Virus Type 1 (HIV-1) Gene Expression and Virus Production by an HIV-2 Tat Activation-Response RNA Decoy

Catherine M. Browning,1 Laurence Cagnon,2 Paul D. Good,3 John Rossi,2 David R. Engelke,3 and David M. Markovitz4,*

Department of Microbiology and Immunology,1 Department of Biological Chemistry,3 and Department of Internal Medicine,4 University of Michigan, Ann Arbor, Michigan 48109, and Department of Molecular Biology, Beckman Research Institute of the City of Hope, Duarte, California 910102

Received 2 November 1998/Accepted 28 February 1999

Tat activation-response region (TAR) decoys have been developed for use in gene therapy for people infected with human immunodeficiency virus type 1 (HIV-1). When a TAR RNA decoy is overexpressed, it will bind Tat, thus leaving less of this crucial protein to bind to and activate the natural transcriptional promoter of HIV-1. Previous TAR decoy constructs have used HIV-1 TAR. However, recent epidemiological and biological data began to suggest that the TAR region from the human immunodeficiency virus type 2 (HIV-2) may suppress HIV-1 transcription and hence replication. We created a vector which overexpresses TAR-2 under the control of the human U6 small nuclear RNA gene promoter and here show that the U6-TAR-2 decoy construct potently inhibits both HIV-2 and HIV-1 gene expression. Further, this decoy construct is able to markedly suppress HIV-1 replication. Thus, we have directly proven that TAR-2 can suppress HIV-1 replication and suggest that the HIV-2 TAR decoy may prove useful for combating HIV-1 infection.

* Corresponding author. Mailing address: 5220 MSRB III, University of Michigan Medical Center, 1150 W. Medical Center Dr., Ann Arbor, MI 48109-0640. Phone: (734) 647-1786. Fax: (734) 764-0101. E-mail: DMARKOV{at}UMICH.EDU.

Journal of Virology, June 1999, p. 5191-5195, Vol. 73, No. 6
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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