Turmeric curcumin inhibits entry of all hepatitis C virus genotypes into human liver cells
Turmeric curcumin inhibits entry of all hepatitis C virus genotypes into human liver cells
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DOI：
10.1136/gutjnl-2012-304299
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发表时间：
2014-07-01
期刊：
影响因子：
24.5
通讯作者：
Steinmann, Eike
中科院分区：
文献类型：
--
作者：
Anggakusuma;Colpitts, Che C.;Steinmann, Eike
目的丙型肝炎病毒（HCV）感染导致严重的肝脏疾病，影响全球超过1.6亿人。肝移植患者普遍面临移植物再感染的问题。因此，迫切需要针对感染早期阶段的负担得起的抗病毒策略，以防止丙型肝炎病毒感染的复发。该研究的目的是确定姜黄素作为HCV进入抑制剂的效力。采用HCV伪颗粒（HCVpp）和细胞培养源性HCV （HCVcc）对肝癌细胞系和人原代肝细胞进行抗病毒活性评价。利用r18标记病毒粒子和膜流动性试验分析了其作用机制。结果姜黄素治疗对HCV RNA复制和病毒组装/释放无影响。然而，HCV与姜黄素共孵育可有效抑制所有主要HCV基因型的进入。其他姜黄素衍生物也有类似的抗病毒活性，但四氢姜黄素没有，这表明α、β不饱和酮群对抗病毒活性的重要性。已知HCV受体的表达水平未发生改变，而用该化合物预处理病毒可降低病毒的感染性，而不发生病毒裂解。膜流动性实验表明，姜黄素影响HCV包膜的流动性，从而损害病毒的结合和融合。姜黄素还被发现可以抑制细胞间传播，并与其他抗病毒药物联合使用。结论姜黄素通过影响肝细胞膜的流动性，从而抑制病毒的结合和融合，从而独立于基因型抑制HCV进入人原代肝细胞。
Objective Hepatitis C virus (HCV) infection causes severe liver disease and affects more than 160 million individuals worldwide. People undergoing liver organ transplantation face universal re-infection of the graft. Therefore, affordable antiviral strategies targeting the early stages of infection are urgently needed to prevent the recurrence of HCV infection. The aim of the study was to determine the potency of turmeric curcumin as an HCV entry inhibitor.Design The antiviral activity of curcumin and its derivatives was evaluated using HCV pseudo-particles (HCVpp) and cell-culture-derived HCV (HCVcc) in hepatoma cell lines and primary human hepatocytes. The mechanism of action was dissected using R18-labelled virions and a membrane fluidity assay.Results Curcumin treatment had no effect on HCV RNA replication or viral assembly/release. However, co-incubation of HCV with curcumin potently inhibited entry of all major HCV genotypes. Similar antiviral activities were also exerted by other curcumin derivatives but not by tetrahydrocurcumin, suggesting the importance of alpha,beta-unsaturated ketone groups for the antiviral activity. Expression levels of known HCV receptors were unaltered, while pretreating the virus with the compound reduced viral infectivity without viral lysis. Membrane fluidity experiments indicated that curcumin affected the fluidity of the HCV envelope resulting in impairment of viral binding and fusion. Curcumin has also been found to inhibit cell-to-cell transmission and to be effective in combination with other antiviral agents.Conclusions Turmeric curcumin inhibits HCV entry independently of the genotype and in primary human hepatocytes by affecting membrane fluidity thereby impairing virus binding and fusion.