title: Antiviral activity of chemical compound isolated from Artemisia morrisonensis against hepatitis B virus in vitro.
abstract: The compound p-hydroxyacetophenone (PHAP) isolated from Artemisia morrisonensis was found to have potential anti-HBV effects in HepG2 2.2.15 cells. We clarified its antiviral mode further and HBV-transfected Huh7 cells were used as the platform. During viral gene expression, treatment with PHAP had no apparent effects on the viral precore/pregenomic RNA. However, the 2.4-kb preS RNA of viral surface gene increased significantly relative to the 2.1-kb S RNA with PHAP. Promoter activity analysis demonstrated that PHAP had a potent effect on augmenting the viral preS promoter activity. The subsequent increase in the large surface protein and induce endoplasmic reticular (ER) stress has been reported previously. Interestingly, PHAP specifically reduced ER stress related GRP78 RNA/protein levels, but not those of GRP94, in treated Huh7 cells while PHAP also led to the significant intracellular accumulation of virus. Moreover, treatment with the ER chaperone inducer thapsigargin relieved the inhibitory effect of PHAP based on the supernatant HBV DNA levels of HBV-expressed cells. In conclusion, this study suggests that the mechanism of HBV inhibition by PHAP might involve the regulation of viral surface gene expression and block virion secretion by interference with the ER stress signaling pathway.
authors.affiliation: Graduate Institute of Ecology and Evolutionary Biology and Research Center for Biodiversity, China Medical University, Taichung, Taiwan.
authors.forename: Tsurng-Juhn
authors.initials: TJ
authors.lastname: Huang
authors.affiliation: Graduate Institute of Ecology and Evolutionary Biology and Research Center for Biodiversity, China Medical University, Taichung, Taiwan.
authors.forename: Shu-Heng
authors.initials: SH
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan; Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung, Taiwan.
authors.forename: Yu-Cheng
authors.initials: YC
authors.lastname: Kuo
authors.affiliation: Department of Anesthesiology, China Medical University Hospital, Taichung, Taiwan; School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Chia-Wen
authors.initials: CW
authors.lastname: Chen
authors.affiliation: Graduate Institute of Ecology and Evolutionary Biology and Research Center for Biodiversity, China Medical University, Taichung, Taiwan. Electronic address: scc@mail.cmu.edu.tw.
authors.forename: Shen-Chieh
authors.initials: SC
authors.lastname: Chou
mesh_terms: D000098:Acetophenones / Q000302:isolation & purification / Q000494:pharmacology*; D000998:Antiviral Agents / Q000302:isolation & purification / Q000494:pharmacology*; D019306:Artemisia / Q000737:chemistry*; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000502:physiology; D000091342:Endoplasmic Reticulum Chaperone BiP; D006514:Hepatitis B Surface Antigens / Q000096:biosynthesis; D006515:Hepatitis B virus / Q000187:drug effects*; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D013312:Stress, Physiological; D015533:Transcriptional Activation / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000098:Acetophenones; D000998:Antiviral Agents; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006514:Hepatitis B Surface Antigens; D010936:Plant Extracts; C031335:4-hydroxyacetophenone
keywords: Artemisia morrisonensis; ER stress; HepG2 2.2.15 cell; Hepatitis B virus; Huh7 cell; p-Hydroxyacetophenone