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Inhibition of hepatitis C virus replication through adenosine monophosphate‐activated protein kinase‐dependent and ‐independent pathways
Author(s) -
Nakashima Kenji,
Takeuchi Kenji,
Chihara Kazuyasu,
Hotta Hak,
Sada Kiyonao
Publication year - 2011
Publication title -
microbiology and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.664
H-Index - 70
eISSN - 1348-0421
pISSN - 0385-5600
DOI - 10.1111/j.1348-0421.2011.00382.x
Subject(s) - ampk , protein kinase a , metformin , activator (genetics) , biology , hepatitis c virus , amp activated protein kinase , adenosine monophosphate , cell culture , kinase , viral replication , medicine , endocrinology , adenosine , microbiology and biotechnology , virus , virology , diabetes mellitus , biochemistry , receptor , genetics
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.