ICP0 dismantles microtubule networks in herpes simplex virus-infected cells.
ICP0 dismantles microtubule networks in herpes simplex virus-infected cells.
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DOI：
10.1371/journal.pone.0010975
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发表时间：
2010-06-08
期刊：
影响因子：
3.7
通讯作者：
Halford WP
中科院分区：
文献类型：
--
作者：
Liu M;Schmidt EE;Halford WP
单核细胞蛋白0（ICP 0）是一种环指E3连接酶，调节单纯疱疹病毒（HSV）mRNA的合成，并强烈影响HSV潜伏期和复制之间的平衡。25年来，ICP 0的核功能一直受到严格审查。为了获得ICP 0作用机制的新线索，我们构建了表达GFP标记的ICP 0的HSV-1病毒。令我们惊讶的是，GFP标记的和野生型ICP 0主要在HSV感染细胞的细胞质中观察到。虽然ICP 0在HSV感染的早期阶段仅在细胞核内，但进一步的分析表明，ICP 0在早期阶段转移到细胞质中，在那里它触发了以前未被识别的过程; ICP 0拆除了宿主细胞的微管网络。ICP 0的RING指突变体有效地捆绑微管，但未能分散微管束。ICP 0的合成被证明是必要的和足够的破坏微管网络在HSV感染和转染的细胞。动植物病毒编码许多重组微管的蛋白质。然而，这是第一次报告的病毒E3连接酶，调节微管的稳定性。有趣的是，几种细胞E3连接酶在有丝分裂过程中协调微管的拆卸和重新组装。我们的研究结果表明，ICP 0在HSV生命周期中起双重作用，首先作为病毒mRNA合成的核调节因子，然后在细胞质中拆除宿主细胞的微管网络，为病毒体合成和/或外出做准备。
Infected-cell protein 0 (ICP0) is a RING finger E3 ligase that regulates herpes simplex virus (HSV) mRNA synthesis, and strongly influences the balance between latency and replication of HSV. For 25 years, the nuclear functions of ICP0 have been the subject of intense scrutiny. To obtain new clues about ICP0's mechanism of action, we constructed HSV-1 viruses that expressed GFP-tagged ICP0. To our surprise, both GFP-tagged and wild-type ICP0 were predominantly observed in the cytoplasm of HSV-infected cells. Although ICP0 is exclusively nuclear during the immediate-early phase of HSV infection, further analysis revealed that ICP0 translocated to the cytoplasm during the early phase where it triggered a previously unrecognized process; ICP0 dismantled the microtubule network of the host cell. A RING finger mutant of ICP0 efficiently bundled microtubules, but failed to disperse microtubule bundles. Synthesis of ICP0 proved to be necessary and sufficient to disrupt microtubule networks in HSV-infected and transfected cells. Plant and animal viruses encode many proteins that reorganize microtubules. However, this is the first report of a viral E3 ligase that regulates microtubule stability. Intriguingly, several cellular E3 ligases orchestrate microtubule disassembly and reassembly during mitosis. Our results suggest that ICP0 serves a dual role in the HSV life cycle, acting first as a nuclear regulator of viral mRNA synthesis and acting later, in the cytoplasm, to dismantle the host cell's microtubule network in preparation for virion synthesis and/or egress.
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