title: Inhibition of hepatitis C virus replication through adenosine monophosphate-activated protein kinase-dependent and -independent pathways.
abstract: Persistent infection with hepatitis C virus (HCV) is closely correlated with type 2 diabetes. In this study, replication of HCV at different glucose concentrations was investigated by using J6/JFH1-derived cell-adapted HCV in Huh-7.5 cells and the mechanism of regulation of HCV replication by AMP-activated protein kinase (AMPK) as an energy sensor of the cell analyzed. Reducing the glucose concentration in the cell culture medium from 4.5 to 1.0 g/L resulted in suppression of HCV replication, along with activation of AMPK. Whereas treatment of cells with AMPK activator 5-aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR) suppressed HCV replication, compound C, a specific AMPK inhibitor, prevented AICAR's effect, suggesting that AICAR suppresses the replication of HCV by activating AMPK in Huh-7.5 cells. In contrast, compound C induced further suppression of HCV replication when the cells were cultured in low glucose concentrations or with metformin. These results suggest that low glucose concentrations and metformin have anti-HCV effects independently of AMPK activation.
authors: Division of Microbiology, Department of Pathological Sciences, Faculty of Medical Sciences, Kobe University Graduate School of Medicine, Kobe, Japan.
authors: Kenji
authors: K
authors: Nakashima
authors: Kenji
authors: K
authors: Takeuchi
authors: Kazuyasu
authors: K
authors: Chihara
authors: Hak
authors: H
authors: Hotta
authors: Kiyonao
authors: K
authors: Sada
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D002460:Cell Line; D003470:Culture Media / Q000737:chemistry; D005947:Glucose / Q000378:metabolism; D016174:Hepacivirus / Q000254:growth & development / Q000502:physiology*; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D008687:Metformin / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D003470:Culture Media; D008687:Metformin; D011494:Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases; D005947:Glucose