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.