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

Hye Jeong Cho, Fuqu Yu, Ren Sun, Dongho Lee, Moon Jung Song

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8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1517-1525
Number of pages9
JournalArchives of Virology
Volume153
Issue number8
DOIs
Publication statusPublished - 2008 Aug 1

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Primary Effusion Lymphoma
Human Herpesvirus 8
Biological Products
Screening
Genes
Fluorescence
Throughput
Tumors
Cells
Bioassay
Rapid thermal annealing
Plant Extracts
Reporter Genes
Gene expression
Antiviral Agents
Gene Expression
Neoplasms
Kaposi's Sarcoma
Viral Genome
Biological Assay

ASJC Scopus subject areas

  • Genetics
  • Applied Microbiology and Biotechnology

Cite this

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title = "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",
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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AU - Cho, Hye Jeong

AU - Yu, Fuqu

AU - Sun, Ren

AU - Lee, Dongho

AU - Song, Moon Jung

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N2 - 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.

AB - 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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