TY - JOUR
T1 - 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
AU - Cho, Hye Jeong
AU - Yu, Fuqu
AU - Sun, Ren
AU - Lee, Dongho
AU - Song, Moon Jung
N1 - Funding Information:
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).
PY - 2008/8
Y1 - 2008/8
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.
UR - http://www.scopus.com/inward/record.url?scp=47549119646&partnerID=8YFLogxK
U2 - 10.1007/s00705-008-0144-4
DO - 10.1007/s00705-008-0144-4
M3 - Article
C2 - 18607675
AN - SCOPUS:47549119646
SN - 0304-8608
VL - 153
SP - 1517
EP - 1525
JO - Archives of virology
JF - Archives of virology
IS - 8
ER -