Antiviral activity of glycyrrhizin against hepatitis C virus in vitro.
Antiviral activity of glycyrrhizin against hepatitis C virus in vitro.
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DOI：
10.1371/journal.pone.0068992
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Aizaki H
中科院分区：
文献类型：
--
作者：
Matsumoto Y;Matsuura T;Aoyagi H;Matsuda M;Hmwe SS;Date T;Watanabe N;Watashi K;Suzuki R;Ichinose S;Wake K;Suzuki T;Miyamura T;Wakita T;Aizaki H
甘草酸（GL）已在日本用于治疗慢性病毒性肝炎患者，作为抗炎药，以降低血清丙氨酸氨基转移酶水平。已知GL还表现出多种生物活性，包括抗病毒作用，但GL的抗丙型肝炎病毒（HCV）作用仍有待阐明。在这项研究中，我们证明了GL治疗HCV感染的Huh7细胞导致感染性HCV的生产减少使用细胞培养产生的HCV（HCV3）。为了确定GL的HCV生命周期中的目标步骤，我们使用了HCV假颗粒（HCVpp）、复制子和HCVpp系统。未观察到病毒进入和复制步骤的显著支持。有趣的是，细胞外感染性降低，细胞内感染性增加。通过免疫荧光和电子显微镜分析GL处理的细胞，HCV核心抗原和电子致密颗粒分别聚集在附着于脂滴（LD）的内质网上，这被认为是HCV组装的平台。此外，LD组分中HCV核心抗原的量增加。总之，这些结果表明GL抑制感染性HCV颗粒的释放。已知GL对磷脂酶A2（PLA2）具有抑制作用。我们发现，1B组PLA2（PLA2G1B）抑制剂也减少了HCV的释放，这表明GL治疗抑制病毒释放可能是由于其对PLA2G1B的抑制作用。最后，我们证明了与GL的组合处理增强了IFN诱导的HCVRNA系统中病毒的减少。GL被鉴定为一种新型抗HCV药物，靶向感染性病毒颗粒释放。
Glycyrrhizin (GL) has been used in Japan to treat patients with chronic viral hepatitis, as an anti-inflammatory drug to reduce serum alanine aminotransferase levels. GL is also known to exhibit various biological activities, including anti-viral effects, but the anti-hepatitis C virus (HCV) effect of GL remains to be clarified. In this study, we demonstrated that GL treatment of HCV-infected Huh7 cells caused a reduction of infectious HCV production using cell culture-produced HCV (HCVcc). To determine the target step in the HCV lifecycle of GL, we used HCV pseudoparticles (HCVpp), replicon, and HCVcc systems. Significant suppressions of viral entry and replication steps were not observed. Interestingly, extracellular infectivity was decreased, and intracellular infectivity was increased. By immunofluorescence and electron microscopic analysis of GL treated cells, HCV core antigens and electron-dense particles had accumulated on endoplasmic reticulum attached to lipid droplet (LD), respectively, which is thought to act as platforms for HCV assembly. Furthermore, the amount of HCV core antigen in LD fraction increased. Taken together, these results suggest that GL inhibits release of infectious HCV particles. GL is known to have an inhibitory effect on phospholipase A2 (PLA2). We found that group 1B PLA2 (PLA2G1B) inhibitor also decreased HCV release, suggesting that suppression of virus release by GL treatment may be due to its inhibitory effect on PLA2G1B. Finally, we demonstrated that combination treatment with GL augmented IFN-induced reduction of virus in the HCVcc system. GL is identified as a novel anti-HCV agent that targets infectious virus particle release.
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影响因子：
2.5
作者：
Manns MP;Wedemeyer H;Singer A;Khomutjanskaja N;Dienes HP;Roskams T;Goldin R;Hehnke U;Inoue H;European SNMC Study Group
通讯作者：
European SNMC Study Group
影响因子：
7.4
作者：
Ashfaq UA;Masoud MS;Nawaz Z;Riazuddin S
通讯作者：
Riazuddin S
影响因子：
7.6
作者：
CRANCE, JM;LEVEQUE, F;DELOINCE, R
通讯作者：
DELOINCE, R
影响因子：
5.4
作者：
Harada, H;Suzu, S;Okada, S
通讯作者：
Okada, S
影响因子：
3.9
作者：
McLauchlan, John
通讯作者：
McLauchlan, John