West Nile virus genome amplification requires the functional activities of the proteasome
West Nile virus genome amplification requires the functional activities of the proteasome
复制标题
DOI：
10.1016/j.virol.2008.11.034
复制
发表时间：
2009-03-01
期刊：
影响因子：
3.7
通讯作者：
Mason, Peter W.
中科院分区：
文献类型：
--
作者：
Gilfoy, Felicia;Fayzulin, Rafik;Mason, Peter W.
细胞内病原体，特别是病毒的生命周期与其宿主细胞的大分子合成过程密切相关。在正链RNA病毒的情况下，翻译并因此复制其感染基因组的能力取决于劫持宿主蛋白。为了鉴定参与西尼罗河病毒（WNV）复制的蛋白质，我们测试了设计用于敲低大的人类基因子集的表达以干扰WNV复制子的复制的siRNA的能力。在这里，我们报告，多个siRNA的蛋白酶体亚基干扰西尼罗河病毒基因组扩增。通过证明沉默蛋白酶体亚基不干扰委内瑞拉马脑炎病毒复制子来显示干扰的特异性。阻断蛋白酶体活性的药物是WNV基因组扩增的有效抑制剂，即使在感染后12小时处理细胞，这表明蛋白酶体在WNV感染周期的进入后阶段是必需的。(c)2008年爱思唯尔公司All rights reserved.
The lifecycle of intracellular pathogens, especially viruses, is intimately tied to the macromolecular synthetic processes of their host cell. In the case of positive-stranded RNA viruses, the ability to translate and, thus, replicate their infecting genome is dependent upon hijacking host proteins. To identify proteins that participate in West Nile virus (WNV) replication, we tested the ability of siRNAs designed to knock-down the expression of a large subset of human genes to interfere with replication of WNV replicons. Here we report that multiple siRNAs for proteasome subunits interfered with WNV genome amplification. Specificity of the interference was shown by demonstrating that silencing proteasome subunits did not interfere with Venezuelan equine encephalitis virus replicons. Drugs that blocked proteasome activity were potent inhibitors of WNV genome amplification even if cells were treated 12 h after infection, indicating that the proteasome is required at a post-entry stage(s) of the WNV infection cycle. (c) 2008 Elsevier Inc. All rights reserved.