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Updated: May 1, 2026

Development of a Hepatitis B Virus Reporter System to Monitor the Early Stages of the Replication Cycle
Published on: February 1, 2017
A new compound from Micromonospora sp. SA246, 9-hydroxycrisamicin-A, activates hepatitis B virus replication
Seok Won Yoon1, In Young Park, Bo Hwa Sohn
1Liver Cell Signal Transduction Laboratory, Bioscience Research Division, Korea Research Institute of Bioscience and Biotechnology, P.O. Box 115, Yusong, Taejon 305-600, Republic of Korea.
Abstract:
A new compound from Micromonospora sp. SA246, 9-hydroxycrisamicin-A (9-HCA-A), showed potential for activating hepatitis B virus (HBV) replication. To define the mechanism of 9-HCA-A, we used HepG2 2.2.15 cells which support HBV replication. 9-HCA-A activated HBV replication, increased episomal and integrated HBV DNA content, and increased secretions of HBV antigens (HBsAg and HBeAg) into culture medium. 9-HCA-A also activated HBV transcription in Hep2 2.2.15 cell line. To examine transcriptional control mechanisms, we analyzed the effect of 9-HCA-A on four different HBV promoters (Core, PreS1, PreS2, and X) in hepatoma cell line. 9-HCA-A responsive element was located at HBx promoter. By EMSA, we showed that 9-HCA-A activated the HBx promoter by detaching the 9-HCA-A responsive element binding protein (9H-REBP). Protein phosphatase (PP2A1) treatment detaches the 9H-REBP from the HBx promoter, similar to 9-HCA-A, while protein kinase A treatment does not detach the 9H-REBP from the HBx promoter. Our results showed that 9H- REBP functions as a repressor of HBV replication while 9-HCA-A activated protein phosphatase released the BP on the HBx promoter, thus activating HBV replication.
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