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Lytic induction of Kaposi’s sarcoma-associated herpesvirus in primary effusion lymphoma cells with natural products identified by a cell-based fluorescence moderate-throughput screening

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Abstract

Kaposi’s sarcoma-associated herpesvirus (KSHV) has been linked to Kaposi’s sarcoma primary effusion lymphoma (PEL), and multicentric Castleman’s disease. Intentional lytic induction of gammaherpesviruses in the presence of antiviral drugs is thought to be an effective treatment option for gammaherpesvirus-related tumors. In this study, we used a cell-based fluorescence bioassay system in which a KSHV-infected PEL cell line was stably transfected with a potent viral-promoter-driven reporter gene to identify effective non-toxic reagents capable of inducing latent KSHV. Among 400 plant extracts screened, three extracts increased reporter gene expression in a dose-dependent manner. Furthermore, the three extracts activated the RTA promoter and induced expression of lytic genes in the endogenous viral genomes of KSHV-infected tumor cells. Together, our results demonstrate the effectiveness of a moderate-throughput screening system to identify natural products capable of inducing KSHV reactivation, thereby facilitating the development of novel therapeutic agents for KSHV-associated malignancies.

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Acknowledgments

The authors would like to thank Dr. Yunkyun Kim (Dankuk University, Korea) for calculating the EC50 values and Ms. Nahyun Kim (Korea University) for measuring phorbol ester levels in the natural products. This work was supported by grants to M.J.S. from the Korean Ministry of Education and Human Resources Development (2006).

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Authors and Affiliations

  1. Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, West building Rm 303, 136-713, Seoul, Republic of Korea

    Hye-Jeong Cho, Dongho Lee & Moon Jung Song

  2. Department of Molecular and Medical Pharmacology, University of California at Los Angeles, Los Angeles, CA, 90095, U.S.A

    Fuqu Yu & Ren Sun

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  1. Hye-Jeong Cho
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  2. Fuqu Yu
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Correspondence to Moon Jung Song.

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Cho, HJ., Yu, F., Sun, R. et al. Lytic induction of Kaposi’s sarcoma-associated herpesvirus in primary effusion lymphoma cells with natural products identified by a cell-based fluorescence moderate-throughput screening. Arch Virol 153, 1517–1525 (2008). https://doi.org/10.1007/s00705-008-0144-4

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  • DOI: https://doi.org/10.1007/s00705-008-0144-4

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