Valosin-containing protein (VCP/p97) plays a role in the replication of West Nile virus.
Valosin-containing protein (VCP/p97) plays a role in the replication of West Nile virus.
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DOI：
10.1016/j.virusres.2016.11.029
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发表时间：
2017-01-15
期刊：
影响因子：
5
通讯作者：
Sawa H
中科院分区：
文献类型：
--
作者：
Phongphaew W;Kobayashi S;Sasaki M;Carr M;Hall WW;Orba Y;Sawa H
化学抑制剂抑制VCP以剂量依赖的方式降低西尼罗河病毒感染。用siRNA敲低内源性VCP水平抑制西尼罗河病毒感染。在西尼罗河病毒复制周期的早期阶段，VCP水平的降低抑制了西尼罗河病毒的感染。VCP水平的降低降低了新生西尼罗河病毒基因组RNA。VCP参与早期阶段和病毒基因组RNA复制。Valosin-containing protein （VCP）被归类为II型AAA+ atp酶蛋白家族的一员。VCP在多种细胞过程中起作用，包括蛋白质降解、膜融合、囊泡运输和应力颗粒的分解。此外，VCP被认为在几种病毒的复制中发挥作用，尽管通过不同的机制。在本研究中，我们研究了VCP在西尼罗病毒（WNV）感染中的作用。内源性VCP表达被VCP抑制剂或siRNA敲除抑制。由此可见，抑制内源性VCP表达可显著抑制西尼罗河病毒感染。进入实验显示，与对照sirna处理的细胞相比，内源性VCP沉默导致WNV-RNA表达水平显著降低。这表明VCP可能在WNV生命周期的早期阶段发挥作用，无论是结合阶段还是进入阶段。利用WNV病毒样颗粒和基于WNV- dna的复制子，可以证明VCP表达的扰动降低了新合成的WNV基因组RNA的水平。这些发现表明，VCP参与了西尼罗河病毒生命周期的早期步骤和基因组复制过程。
Inhibition of VCP by chemical inhibitors decreased WNV infection in a dose-dependent manner. Knockdown of endogenous VCP level using siRNA suppressed WNV infection. Depletion of VCP levels suppressed WNV infection at the early stages of WNV replication cycle. Depletion of VCP levels lowered nascent WNV genomic RNA. VCP participates in early stages and viral genomic RNA replication. Valosin-containing protein (VCP) is classified as a member of the type II AAA+ ATPase protein family. VCP functions in several cellular processes, including protein degradation, membrane fusion, vesicular trafficking and disassembly of stress granules. Moreover, VCP is considered to play a role in the replication of several viruses, albeit through different mechanisms. In the present study, we have investigated the role of VCP in West Nile virus (WNV) infection. Endogenous VCP expression was inhibited using either VCP inhibitors or by siRNA knockdown. It could be shown that the inhibition of endogenous VCP expression significantly inhibited WNV infection. The entry assay revealed that silencing of endogenous VCP caused a significant reduction in the expression levels of WNV-RNA compared to control siRNA-treated cells. This indicates that VCP may play a role in early steps either the binding or entry steps of the WNV life cycle. Using WNV virus like particles and WNV-DNA-based replicon, it could be demonstrated that perturbation of VCP expression decreased levels of newly synthesized WNV genomic RNA. These findings suggest that VCP is involved in early steps and during genome replication of the WNV life cycle.
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DOI：
10.3390/v6010013
发表时间：
2013-12-27
期刊：
Viruses
影响因子：
--
作者：
Brinton MA
通讯作者：
Brinton MA
DOI：
10.1074/jbc.m110.215319
发表时间：
2011-05-13
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Chou TF;Deshaies RJ
通讯作者：
Deshaies RJ
影响因子：
--
作者：
Heinz FX;Allison SL
通讯作者：
Allison SL
影响因子：
5.4
作者：
Ambrose, Rebecca L.;Mackenzie, Jason M.
通讯作者：
Mackenzie, Jason M.
影响因子：
5.4
作者：
Carnec, Xavier;Meertens, Laurent;Amara, Ali
通讯作者：
Amara, Ali