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Antimicrobial Agents and Chemotherapy, September 2005, p. 3833-3841, Vol. 49, No. 9
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.9.3833-3841.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

High-Throughput Human Immunodeficiency Virus Type 1 (HIV-1) Full Replication Assay That Includes HIV-1 Vif as an Antiviral Target

Joan Cao, Jason Isaacson, Amy K. Patick, and Wade S. Blair*

Department of Virology, Pfizer Global Research and Development, La Jolla Laboratories, 10777 Science Center Dr. (CB1), San Diego, California 92121

Received 3 March 2005/ Returned for modification 28 April 2005/ Accepted 26 May 2005

Antiviral screens have proved useful for the identification of novel human immunodeficiency virus type 1 (HIV-1) inhibitors. In this study, we describe an HIV-1 full replication (HIV-1 Rep) assay that incorporates all of the targets required for replication in T-cell lines, including the HIV-1 Vif gene. The HIV-1 Rep assay was designed to exhibit optimal sensitivity to late-stage as well as early-stage inhibitors to maximize the likelihood of identification of novel target antiviral compounds in a screen. In addition, the flexibility of the HIV-1 Rep assay allows the rapid evaluation of antiviral compounds against different virus strains in different T-cell lines without significant modification of the assay format. We demonstrate that the HIV-1 Rep assay exhibits characteristics (e.g., a favorable Z' value) compatible with high-throughput screening in a 384-well format. The utility of the HIV-1 Rep assay was demonstrated in a high-throughput screen of >106 compounds. To our knowledge, this study represents the first example of an HIV-1 antiviral screen that includes Vif as a functional target and was executed on an industrial scale.

* Corresponding author. Mailing address: Department of Virology, Pfizer Global Research and Development, La Jolla Laboratories, 10777 Science Center Dr. (CB1), San Diego, CA 92121-1111. Phone: (858) 622-7692. Fax: (858) 526-4451. E-mail: wade.blair{at}pfizer.com.

Antimicrobial Agents and Chemotherapy, September 2005, p. 3833-3841, Vol. 49, No. 9
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.9.3833-3841.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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