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【文摘发布】[Hepatology]利用RNA干扰技术鉴定HCV复
题目：Identification of host genes involved in hepatitis C virus replication by small interfering RNA technology.
作者：Ng TI, Mo H, Pilot-Matias T, He Y,et al.
摘要：Hepatitis C virus (HCV) replication is highly dependent on host cell factors. Identification of these host factors not only facilitates understanding of the biology of HCV infection but also enables the discovery of novel targets for anti-HCV therapy. To identify host genes important for HCV RNA replication, we screened a library of small interfering RNA (siRNA) that targets approximately 4,000 human genes in Huh7-derived EN5-3 cells harboring an HCV subgenomic replicon with the nonstructural region NS3-NS5B from the 1b-N strain. Nine cellular genes that potentially regulate HCV replication were identified in this screen. Silencing of these genes resulted in inhibition of HCV replication by more than 60% and exhibited minimal toxicity. Knockdown of host gene expression by these siRNAs was confirmed at the RNA level and, in some instances, at the protein level. The level of siRNA silencing of these host genes correlated well with inhibition of HCV. These genes included those that encoded a G-protein coupled receptor (TBXA2R), a membrane protein (LTbeta), an adapter protein (TRAF2), 2 transcription factors (RelA and NFkappaB2), 2 protein kinases (MKK7 and SNARK), and 2 closely related transporter proteins (SLC12A4 and SLC12A5). Of interest, some of these genes are members of the tumor necrosis factor/lymphotoxin signaling pathway. Conclusion: Findings of this study may provide important information for understanding HCV replication. In addition, these cellular genes may constitute a novel set of targets for HCV antiviral therapy.
PMID: 17518369 本人已认领该文编译，48小时后若未提交译文，请其他战友自由认领。 来源：Hepatology. 2007 May 22;
来源：肝病学。2007年5月22日；
题目：Identification of host genes involved in hepatitis C virus replication by small interfering RNA technology.
题目：利用RNA干扰技术鉴定参与HCV复制的宿主基因
作者：Ng TI, Mo H, Pilot-Matias T, He Y,et al.
摘 要：Hepatitis C virus (HCV) replication is highly dependent on host cell factors. Identification of these host factors not only facilitates understanding of the biology of HCV infection but also enables the discovery of novel targets for anti-HCV therapy. To identify host genes important for HCV RNA replication, we screened a library of small interfering RNA (siRNA) that targets approximately 4,000 human genes in Huh7-derived EN5-3 cells harboring an HCV subgenomic replicon with the nonstructural region NS3-NS5B from the 1b-N strain. Nine cellular genes that potentially regulate HCV replication were identified in this screen. Silencing of these genes resulted in inhibition of HCV replication by more than 60% and exhibited minimal toxicity. Knockdown of host gene expression by these siRNAs was confirmed at the RNA level and, in some instances, at the protein level. The level of siRNA silencing of these host genes correlated well with inhibition of HCV. These genes included those that encoded a G-protein coupled receptor (TBXA2R), a membrane protein (LTbeta), an adapter protein (TRAF2), 2 transcription factors (RelA and NFkappaB2), 2 protein kinases (MKK7 and SNARK), and 2 closely related transporter proteins (SLC12A4 and SLC12A5). Of interest, some of these genes are members of the tumor necrosis factor/lymphotoxin signaling pathway. Conclusion: Findings of this study may provide important information for understanding HCV replication. In addition, these cellular genes may constitute a novel set of targets for HCV antiviral therapy.
HCV复制高度依赖于宿主的细胞因素。鉴定这些宿主因素不但有助于理解HCV感染生物学，而且有助于发现治疗HCV的新靶点。为了鉴定对HCV RNA复制有重要意义的宿主基因，我们筛选了源于Huh7的EN5-3细胞中的近4000条人类基因的小干扰RNA库（siRNA），EN5-3细胞可将HCV亚基因组复制子停泊于1b-N株的NS3-NS5B区（没做过类似的试验，所以翻译可能有所出入，请高手指正）。在本筛选中我们鉴定了可能调节HCV复制的9条基因。使这些基因沉默可以导致HCV复制减少超过60%，而且细胞毒性降到最低。以这些siRNA敲除宿主基因表达在RNA水平得以证实，在某些情况下，可在蛋白水平证实。siRNA使宿主基因沉默程度与HCV的抑制性相关性良好。这些基因包括一种G蛋白偶联受体(TBXA2R)、一种膜蛋白(LTbeta)、一种接头蛋白(TRAF2)、两种转录因子（RelA和核因子κB2），两种蛋白激酶（MKK4和SNARK）和两种密切相关的转录蛋白(SLC12A4和SLC12A5)的编码基因。有趣的是，这些基因中有部分基因参与了肿瘤坏死因子/淋巴毒素的信号转导通路。结论：本研究结果可为明确HCV复制提供重要信息。此外，这些细胞的基因可以成为治疗HCV的一系列新靶点。
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作者:admin@医学,生命科学 2011-02-23 05:12
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