Hsp90 inhibitors suppress HCV replication in replicon cells and humanized liver mice
Hsp90 inhibitors suppress HCV replication in replicon cells and humanized liver mice
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DOI：
10.1016/j.bbrc.2006.12.117
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发表时间：
2007-02-23
影响因子：
3.1
通讯作者：
Kohara, Michinori
中科院分区：
文献类型：
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作者：
Nakagawa, Shin-ichiro;Umehara, Takuya;Kohara, Michinori
丙型肝炎病毒（HCV）持续感染是慢性肝炎、肝硬化和肝细胞癌等肝脏疾病的主要原因。在这里，我们报告，抑制热休克蛋白90（Hsp 90）是非常有效的抑制HCV基因组复制。在HCV复制子细胞中，通过Hsp 90抑制剂和通过小干扰RNA（siRNA）介导的内源性Hsp 90表达的敲低来减少HCV复制。通过用Hsp 90表达载体转染来防止Hsp 90抑制剂对HCV复制的抑制。我们还测试了Hsp 90抑制在具有人源化肝脏的HCV感染的嵌合小鼠中的抗HCV效果。Hsp 90抑制剂和聚乙二醇结合的干扰素（PEG-IFN）联合给药在降低血清中HCV基因组RNA水平方面比PEG-IFN单药治疗更有效。这些结果表明，抑制Hsp 90可能提供一种新的治疗HCV感染的方法。(c)2006年爱思唯尔公司All rights reserved.
Persistent infection with hepatitis C virus (HCV) is a major cause of liver diseases such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Here we report that inhibition of heat shock protein 90 (Hsp90) is highly effective in suppressing HCV genome replication. In HCV replicon cells, HCV replication was reduced by Hsp90 inhibitors and by knockdown of endogenous Hsp90 expression mediated by small-interfering RNA (siRNA). The suppression of HCV replication by an Hsp90 inhibitor was prevented by transfection with Hsp90 expression vector. We also tested the anti-HCV effect of Hsp90 inhibition in HCV-infected chimeric mice with humanized liver. Combined administration of an Hsp90 inhibitor and polyethylene glycol-conjugated interferon (PEG-IFN) was more effective in reducing HCV genome RNA levels in serum than was PEG-IFN monotherapy. These results suggest that inhibition of Hsp90 could provide a new therapeutic approach to HCV infection. (c) 2006 Elsevier Inc. All rights reserved.