A new compound from Micromonospora sp. SA246, 9-hydroxycrisamicin-A, activates hepatitis B virus replication.
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.
Yoon
Seok Won
SW
Liver 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.
Park
In Young
IY
Sohn
Bo Hwa
BH
Lee
Jaehyouk
J
Yeo
Woon Hyung
WH
Lee
Young Ik
YI
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D015967:Gene Expression Regulation, Viral; D006515:Hepatitis B virus / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D008847:Micromonospora / Q000737:chemistry*; D015394:Molecular Structure; D009285:Naphthoquinones / Q000737:chemistry / Q000494:pharmacology*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000502:physiology*
C114119:9-hydroxycrisamicin A; D000900:Anti-Bacterial Agents; D009285:Naphthoquinones; D014764:Viral Proteins; D017868:Cyclic AMP-Dependent Protein Kinases; D010749:Phosphoprotein Phosphatases