• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>PLoS Pathogens >A novel viral strategy for host factor recruitment: The co-opted proteasomal Rpn11 protein interaction hub in cooperation with subverted actin filaments are targeted to deliver cytosolic host factors for viral replication
【24h】

A novel viral strategy for host factor recruitment: The co-opted proteasomal Rpn11 protein interaction hub in cooperation with subverted actin filaments are targeted to deliver cytosolic host factors for viral replication

机译：一种新的宿主因子招聘病毒策略：与颠倒的肌动蛋白细丝合作的共选择蛋白酶体RPN11蛋白相互作用枢纽旨在为病毒复制提供细胞溶质宿主因子

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Positive-strand (+)RNA viruses take advantage of the host cells by subverting a long list of host protein factors and transport vesicles and cellular organelles to build membranous viral replication organelles (VROs) that support robust RNA replication. How RNA viruses accomplish major recruitment tasks of a large number of cellular proteins are intensively studied. In case of tomato bushy stunt virus (TBSV), a single viral replication protein, named p33, carries out most of the recruitment duties. Yet, it is currently unknown how the viral p33 replication protein, which is membrane associated, is capable of the rapid and efficient recruitment of numerous cytosolic host proteins to facilitate the formation of large VROs. In this paper, we show that, TBSV p33 molecules do not recruit each cytosolic host factor one-by-one into VROs, but p33 targets a cytosolic protein interaction hub, namely Rpn11, which interacts with numerous other cytosolic proteins. The highly conserved Rpn11, called POH1 in humans, is the metalloprotease subunit of the proteasome, which couples deubiquitination and degradation of proteasome substrates. However, TBSV takes advantage of a noncanonical function of Rpn11 by exploiting Rpn11’s interaction with highly abundant cytosolic proteins and the actin network. We provide supporting evidence that the co-opted Rpn11 in coordination with the subverted actin network is used for delivering cytosolic proteins, such as glycolytic and fermentation enzymes, which are readily subverted into VROs to produce ATP locally in support of VRO formation, viral replicase complex assembly and viral RNA replication. Using several approaches, including knockdown of Rpn11 level, sequestering Rpn11 from the cytosol into the nucleus in plants or temperature-sensitive mutation in Rpn11 in yeast, we show the inhibition of recruitment of glycolytic and fermentation enzymes into VROs. The Rpn11-assisted recruitment of the cytosolic enzymes by p33, however, also requires the combined and coordinated role of the subverted actin network. Accordingly, stabilization of the actin filaments by expression of the Legionella VipA effector in yeast and plant, or via a mutation of ACT1 in yeast resulted in more efficient and rapid recruitment of Rpn11 and the selected glycolytic and fermentation enzymes into VROs. On the contrary, destruction of the actin filaments via expression of the Legionella RavK effector led to poor recruitment of Rpn11 and glycolytic and fermentation enzymes. Finally, we confirmed the key roles of Rpn11 and the actin filaments in situ ATP production within TBSV VROs via using a FRET-based ATP-biosensor. The novel emerging theme is that TBSV targets Rpn11 cytosolic protein interaction hub driven by the p33 replication protein and aided by the subverted actin filaments to deliver several co-opted cytosolic pro-viral factors for robust replication within VROs.
机译：正链（+）RNA病毒通过对宿主蛋白因子和运输囊泡和细胞细胞器的长期列表来利用宿主细胞来构建支持稳健的RNA复制的膜状病毒复制细胞器（VRO）。 RNA病毒如何完成大量细胞蛋白的主要招聘任务是集中研究的。在番茄浓密的病毒（TBSV）的情况下，一个名为P33的单一病毒复制蛋白，执行大部分招聘职责。然而，目前未知是如何如何快速高效地募集许多细胞溶质宿主蛋白的病毒P33复制蛋白，以便于形成大型VRO的形成。在本文中，我们表明，TBSV P33分子并未逐一将每个细胞溶质宿主因子募集成VRO，但P33靶向细胞溶质蛋白质相互作用枢纽，即RPN11，其与许多其他胞质蛋白相互作用。高度保守的RPN11，称为人类，是蛋白酶体的金属蛋白酶亚基，其致脱硫和蛋白酶体底物的降解。然而，TBSV通过利用RPN11与高丰富的细胞溶质蛋白和肌动蛋白网络进行RPN11的相互作用来利用RPN11的非甘露统称功能。我们提供支持的证据表明，与颠倒的肌动蛋白网络协调的Co-Opted RPN11用于递送细胞溶质蛋白，例如糖酵解和发酵酶，其容易地倒置成VRO，以在典型的副标体中产生ATP，病毒复制酶复合物在局部地局部产生ATP组装和病毒RNA复制。使用几种方法，包括RPN11水平的敲低，从细胞溶溶液中抵消RPN11在酵母中RPN11中的植物中的核心或温度敏感突变中，我们显示抑制糖酵解和发酵酶进入VRO的植物。然而，P33的RPN11辅助募集细胞溶质酶也需要颠倒的肌动蛋白网络的组合和协调作用。因此，通过在酵母和植物中表达致动菌菌菌丝效应器或通过酵母中的ACT1突变稳定肌蛋白长丝导致RPN11和所选糖酵解和发酵酶的更有效和快速募集到VRO中。相反，通过军团菌RACK效应器的表达破坏肌动蛋白细丝导致RPN11和糖酵解和发酵酶的较差较差。最后，我们通过使用基于FRET的ATP-Biosensor确认了RPN11和Actin长丝在TBSV VROS内原位ATP生产的关键作用。新兴的主题是TBSV靶向P33复制蛋白驱动的RPN11细胞溶蛋白相互作用枢纽，并由颠倒的肌动蛋白长丝辅助，以提供几种Co-Opted Cytosolic Pro-病毒因子，用于VRO中的鲁棒复制。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号