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.
authors.affiliation: Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
authors.forename: Hye-Jeong
authors.initials: HJ
authors.lastname: Cho
authors.forename: Fuqu
authors.initials: F
authors.lastname: Yu
authors.forename: Ren
authors.initials: R
authors.lastname: Sun
authors.forename: Dongho
authors.initials: D
authors.lastname: Lee
authors.forename: Moon Jung
authors.initials: MJ
authors.lastname: Song
mesh_terms: D001688:Biological Products / Q000494:pharmacology*; D005453:Fluorescence; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D019288:Herpesvirus 8, Human / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D008223:Lymphoma / Q000473:pathology; D010936:Plant Extracts / Q000494:pharmacology; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D012514:Sarcoma, Kaposi / Q000473:pathology / Q000821:virology*; D014407:Tumor Cells, Cultured; D014779:Virus Replication / Q000187:drug effects* / Q000235:genetics
chemical_list: D001688:Biological Products; D010936:Plant Extracts; D012367:RNA, Viral