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Antimicrobial Agents and Chemotherapy, September 2008, p. 3169-3179, Vol. 52, No. 9
0066-4804/08/$08.00+0     doi:10.1128/AAC.00274-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Heterocyclic Compounds That Inhibit Rev-RRE Function and Human Immunodeficiency Virus Type 1 Replication{triangledown}

Deidra Shuck-Lee,1 Fei Fei Chen,1 Ryan Willard,1 Sharmila Raman,1 Roger Ptak,2 Marie-Louise Hammarskjold,1 and David Rekosh1*

Myles H. Thaler Center for AIDS and Human Retrovirus Research, Department of Microbiology, University of Virginia, Charlottesville, Virginia 22908,1 Southern Research Institute, Department of Infectious Disease Research, Frederick, Maryland 217012

Received 27 February 2008/ Returned for modification 4 May 2008/ Accepted 7 July 2008

A cell-based screening assay was performed to identify compounds that inhibited the postintegration stage of the human immunodeficiency virus (HIV) life cycle. This assay utilized a cell line that contains the HIV gag and pol genes expressed in a Rev-dependent fashion. The cell line produces about 10 to 15 ng of p24 per milliliter of medium over a 24-h period in the form of viruslike particles. Any compound that inhibits a postintegration step in the HIV life cycle scores in this assay by decreasing particle production. Forty thousand compounds were screened, and 192 compounds were selected from the original screen because they showed more than 50% inhibition at a 10 µM concentration. The cumulative evidence presented in this study strongly suggests that 2 of the 192 compounds work as inhibitors of HIV Rev function. This was determined by a variety of cell-based assays, although the compounds do not interfere with Rev-RRE (Rev response element) binding in vitro. Both compounds inhibit replication of the lab isolate NL4-3 as well as an HIV primary isolate from Brazil (93BR021) and thus are promising leads as therapeutic candidates that target HIV replication through inhibition of Rev function.

* Corresponding author. Mailing address: Department of Microbiology, Jordan Hall 7087, P.O. Box 800734, University of Virginia, Charlottesville, VA 22908. Phone: (434) 982-1599. Fax: (434) 982-1590. E-mail: dr4u{at}virginia.edu

{triangledown} Published ahead of print on 14 July 2008.

Antimicrobial Agents and Chemotherapy, September 2008, p. 3169-3179, Vol. 52, No. 9
0066-4804/08/$08.00+0     doi:10.1128/AAC.00274-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Groom, H. C. T., Anderson, E. C., Lever, A. M. L. (2009). Rev: beyond nuclear export. J. Gen. Virol. 90: 1303-1318 [Abstract] [Full Text]  


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