Ac102 Participates in Nuclear Actin Polymerization by Modulating BV/ODV-C42 Ubiquitination during Autographa californica Multiple Nucleopolyhedrovirus Infection
Ac102 Participates in Nuclear Actin Polymerization by Modulating BV/ODV-C42 Ubiquitination during Autographa californica Multiple Nucleopolyhedrovirus Infection
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Ac102 在苜蓿银纹夜蛾多重核多角体病毒感染过程中通过调节 BV/ODV-C42 泛素化参与核肌动蛋白聚合
DOI：
10.1128/jvi.00005-18
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发表时间：
2018
影响因子：
5.4
通讯作者：
Wang Yun
中科院分区：
文献类型：
--
作者：
Zhang Yongli;Hu Xue;Mu Jingfang;Hu Yangyang;Zhou Yuan;Zhao He;Wu Chunchen;Pei Rongjuan;Chen Jizheng;Chen Xinwen;Wang Yun
摘要P78/83作为病毒编码的肌动蛋白成核促进因子（NPF），通过诱导肌动蛋白聚合来辅助苜蓿银纹夜蛾核型多角体病毒（AcMNPV）的增殖。根据我们以前的研究，虽然P78/83积极地经历泛素非依赖性蛋白酶体降解，但AcMNPV编码出芽病毒/闭塞衍生病毒（BV/ODV）-C42（C42），其允许P78/83通过抑制其在病毒感染期间的降解而作为稳定的NPF发挥作用。然而，是否有其他病毒蛋白参与调节P78/83诱导的肌动蛋白聚合尚未确定。在这项研究中，我们发现，Ac 102，一个必不可少的病毒基因产物，以前报道在介导acMNPV感染过程中的肌动蛋白的核积累中发挥关键作用，是一种新的调节P78/83诱导的肌动蛋白聚合。通过表征ac 102敲除的杆粒，我们证明了Ac 102参与调节核肌动蛋白聚合以及核中衣壳结构的形态发生和分布。这些调节作用在很大程度上依赖于Ac 102和C42之间的相互作用。进一步的研究表明，Ac 102与C42结合以抑制C42的K48连接的泛素化，从而减少C42蛋白酶体的降解，从而允许P78/83作为稳定的NPF来诱导肌动蛋白聚合。因此，Ac 102和C42形成一个调节级联来控制病毒NPF活性，代表AcMNPV以泛素依赖性和泛素非依赖性方式协调肌动蛋白聚合的复杂机制。肌动蛋白是真核细胞中功能最重要的蛋白质之一。在形态学上，肌动蛋白可以以两种形式存在：称为球状肌动蛋白（G-肌动蛋白）的单体形式和称为丝状肌动蛋白（F-肌动蛋白）的聚合形式。G-肌动蛋白可以水解成F-肌动蛋白，成核促进因子（NPF）是这一过程的启动剂。许多病毒病原体利用宿主肌动蛋白聚合机制来帮助病毒繁殖。苜蓿银纹夜蛾核型多角体病毒（AcMNPV）诱导宿主细胞内肌动蛋白聚合。P78/83是一种病毒性NPF，负责这一过程。先前，我们鉴定了BV/ODV-C42（C42）与P78/83结合并保护其免于降解。在这份报告中，我们确定了另一种病毒蛋白，Ac 102，参与调节C42泛素化，因此，确保P78/83活性作为NPF启动肌动蛋白聚合。这种调节级联反应代表了一种新的机制，通过这种机制，病毒可以利用细胞肌动蛋白细胞骨架来帮助病毒繁殖。
ABSTRACT As a virus-encoded actin nucleation promoting factor (NPF), P78/83 induces actin polymerization to assist in Autographa californica multiple nucleopolyhedrovirus (AcMNPV) propagation. According to our previous study, although P78/83 actively undergoes ubiquitin-independent proteasomal degradation, AcMNPV encodes budded virus/occlusion derived virus (BV/ODV)-C42 (C42), which allows P78/83 to function as a stable NPF by inhibiting its degradation during viral infection. However, whether there are other viral proteins involved in regulating P78/83-induced actin polymerization has yet to be determined. In this study, we found that Ac102, an essential viral gene product previously reported to play a key role in mediating the nuclear accumulation of actin during AcMNPV infection, is a novel regulator of P78/83-induced actin polymerization. By characterizing an ac102 knockout bacmid, we demonstrated that Ac102 participates in regulating nuclear actin polymerization as well as the morphogenesis and distribution of capsid structures in the nucleus. These regulatory effects are heavily dependent on an interaction between Ac102 and C42. Further investigation revealed that Ac102 binds to C42 to suppress K48-linked ubiquitination of C42, which decreases C42 proteasomal degradation and consequently allows P78/83 to function as a stable NPF to induce actin polymerization. Thus, Ac102 and C42 form a regulatory cascade to control viral NPF activity, representing a sophisticated mechanism for AcMNPV to orchestrate actin polymerization in both a ubiquitin-dependent and ubiquitin-independent manner. IMPORTANCE Actin is one of the most functionally important proteins in eukaryotic cells. Morphologically, actin can be found in two forms: a monomeric form called globular actin (G-actin) and a polymeric form called filamentous actin (F-actin). G-actin can polymerize to form F-actin, and nucleation promoting factor (NPF) is the initiator of this process. Many viral pathogens harness the host actin polymerization machinery to assist in virus propagation. Autographa californica multiple nucleopolyhedrovirus (AcMNPV) induces actin polymerization in host cells. P78/83, a viral NPF, is responsible for this process. Previously, we identified that BV/ODV-C42 (C42) binds to P78/83 and protects it from degradation. In this report, we determined that another viral protein, Ac102, is involved in modulating C42 ubiquitination and, consequently, ensures P78/83 activity as an NPF to initiate actin polymerization. This regulatory cascade represents a novel mechanism by which a virus can harness the cellular actin cytoskeleton to assist in viral propagation.