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Research Articles

Development of a fluorescence-based assay to screen antiviral drugs against Kaposi's sarcoma–associated herpesvirus

¹ Department of Microbiology and Immunology, Lineberger Cancer Center, University of North Carolina at Chapel Hill, North Carolina; ² Natural Products Laboratory, Research Triangle Institute, Research Triangle Park, North Carolina; ³ Program for Collaborative Research in the Pharmaceutical Sciences, Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois; ⁴ University of Papua New Guinea, University Post Office, National Capital District, Papua New Guinea; and ⁵ Tumor Virology Program, Children's Cancer Research Institute, The University of Texas Health Science Center at San Antonio, San Antonio, Texas

Requests for reprints: Blossom Damania, Lineberger Comprehensive Cancer Center, CB no. 7295, University of North Carolina, Chapel Hill, NC 27599. Phone: 919-843-6011; Fax: 919-966-9673. E-mail: damania{at}med.unc.edu

Abstract

Tumors associated with Kaposi's sarcoma–associated herpesvirus infection include Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. Virtually all of the tumor cells in these cancers are latently infected and dependent on the virus for survival. Latent viral proteins maintain the viral genome and are required for tumorigenesis. Current prevention and treatment strategies are limited because they fail to specifically target the latent form of the virus, which can persist for the lifetime of the host. Thus, targeting latent viral proteins may prove to be an important therapeutic modality for existing tumors as well as in tumor prevention by reducing latent virus load. Here, we describe a novel fluorescence-based screening assay to monitor the maintenance of the Kaposi's sarcoma–associated herpesvirus genome in B lymphocyte cell lines and to identify compounds that induce its loss, resulting in tumor cell death. [Mol Cancer Ther 2007;6(8):2360–70]

Grant support: NIH grants CA096500, HL083469, DE018281, and CFAR (2P30AI050410), and an American Heart Association grant 0640041N (B. Damania), NIH grants CA109232 and DE018304, and a Lymphoma Society Translational Science award 6021-06 (D.P. Dittmer). B. Damania is a Leukemia & Lymphoma Society Scholar and Burroughs Welcome Fund Investigator in Infectious Disease. Supported in part by the Virology training grant 5T32AI007419 and Cancer Cell Biology training grant 2T32CA071341 (T.K. Nun). Financial support for the collection and processing of plant materials also came from the NIH (U19-CA52956). Partial support via a Research Scholar Grant from the American Cancer Society RSG-02-024-01-CDD (N.H. Oberlies).

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

⁶ Supplementary material for this article is available at Molecular Cancer Therapeutics Online (http://mct.aacrjournals.org/).

Received 2/16/07; revised 5/16/07; accepted 6/29/07.