Division of Microbiology, Department of Pathological Sciences, Faculty of Medical Sciences, Kobe University Graduate School of Medicine, Kobe, Japan.
Microbiol Immunol. 2011 Nov;55(11):774-82. doi: 10.1111/j.1348-0421.2011.00382.x.
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.
丙型肝炎病毒（HCV）持续感染与 2 型糖尿病密切相关。本研究通过使用 J6/JFH1 衍生的细胞适应 HCV 在 Huh-7.5 细胞中，研究了不同葡萄糖浓度下 HCV 的复制，并分析了 AMP 激活蛋白激酶（AMPK）作为细胞的能量传感器对 HCV 复制的调节机制。将细胞培养物中的葡萄糖浓度从 4.5 降低至 1.0 g/L 会抑制 HCV 复制，并激活 AMPK。虽然用 AMPK 激活剂 5-氨基咪唑-4-甲酰胺 1-β-D-呋喃核糖苷（AICAR）处理细胞可抑制 HCV 复制，但 AMPK 的特异性抑制剂化合物 C 可阻止 AICAR 的作用，表明 AICAR 通过在 Huh-7.5 细胞中激活 AMPK 来抑制 HCV 的复制。相反，当细胞在低糖浓度或二甲双胍存在下培养时，化合物 C 诱导 HCV 复制的进一步抑制。这些结果表明，低糖浓度和二甲双胍具有独立于 AMPK 激活的抗 HCV 作用。
