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1
Three cardiovirus Leader proteins equivalently inhibit four different nucleocytoplasmic trafficking pathways.三种心病毒前导蛋白同等程度地抑制四种不同的核质运输途径。
Virology. 2015 Oct;484:194-202. doi: 10.1016/j.virol.2015.06.004. Epub 2015 Jun 23.
2
Encephalomyocarditis virus leader is phosphorylated by CK2 and syk as a requirement for subsequent phosphorylation of cellular nucleoporins.脑心肌炎病毒前导序列被CK2和syk磷酸化，这是细胞核孔蛋白后续磷酸化的必要条件。
J Virol. 2014 Feb;88(4):2219-26. doi: 10.1128/JVI.03150-13. Epub 2013 Dec 11.
3
Leader-induced phosphorylation of nucleoporins correlates with nuclear trafficking inhibition by cardioviruses.病毒诱导的核孔蛋白磷酸化与心肌病毒引起的核运输抑制相关。
J Virol. 2009 Feb;83(4):1941-51. doi: 10.1128/JVI.01752-08. Epub 2008 Dec 10.
4
Cardiovirus Leader proteins bind exportins: Implications for virus replication and nucleocytoplasmic trafficking inhibition.心病毒前导蛋白与输出蛋白结合：对病毒复制和核质运输抑制的影响。
Virology. 2016 Jan;487:19-26. doi: 10.1016/j.virol.2015.10.001. Epub 2015 Oct 19.
5
Nucleoporin phosphorylation triggered by the encephalomyocarditis virus leader protein is mediated by mitogen-activated protein kinases.脑炎心肌炎病毒衣壳蛋白触发的核孔蛋白磷酸化是由丝裂原活化蛋白激酶介导的。
J Virol. 2010 Dec;84(24):12538-48. doi: 10.1128/JVI.01484-09. Epub 2010 Sep 29.
6
AMP-activated protein kinase phosphorylates EMCV, TMEV and SafV leader proteins at different sites.AMP激活的蛋白激酶在不同位点使脑心肌炎病毒、Theiler小鼠脑脊髓炎病毒和萨菲病毒的前导蛋白磷酸化。
Virology. 2014 Aug;462-463:236-40. doi: 10.1016/j.virol.2014.06.026. Epub 2014 Jul 5.
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Differential Disruption of Nucleocytoplasmic Trafficking Pathways by Rhinovirus 2A Proteases.鼻病毒2A蛋白酶对核质运输途径的差异性破坏
J Virol. 2017 Mar 29;91(8). doi: 10.1128/JVI.02472-16. Print 2017 Apr 15.
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BGLF4 kinase modulates the structure and transport preference of the nuclear pore complex to facilitate nuclear import of Epstein-Barr virus lytic proteins.BGLF4激酶调节核孔复合体的结构和转运偏好，以促进爱泼斯坦-巴尔病毒裂解蛋白的核输入。
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The Leader Protein of Theiler's Virus Prevents the Activation of PKR.西尼罗河病毒的主要结构蛋白可抑制 PKR 的激活。
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Binding interactions between the encephalomyocarditis virus leader and protein 2A.脑心肌炎病毒前导序列与蛋白2A之间的结合相互作用。
J Virol. 2014 Nov;88(22):13503-9. doi: 10.1128/JVI.02148-14. Epub 2014 Sep 10.

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Controlling reactogenicity while preserving immunogenicity from a self-amplifying RNA vaccine by modulating nucleocytoplasmic transport.通过调节核质转运来控制自扩增RNA疫苗的反应原性，同时保留其免疫原性。
NPJ Vaccines. 2025 Apr 29;10(1):85. doi: 10.1038/s41541-025-01135-8.
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Picornavirus security proteins promote the release of extracellular vesicle enclosed viruses via the modulation of host kinases.小核糖核酸病毒结构蛋白通过调节宿主激酶促进含有病毒的细胞外囊泡的释放。
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The nuclear pore protein NUP98 impedes LTR-driven basal gene expression of HIV-1, viral propagation, and infectivity.核孔蛋白 NUP98 可阻碍 HIV-1 的 LTR 驱动的基础基因表达、病毒增殖和感染性。
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Quantitative comparison of nuclear transport inhibition by SARS coronavirus ORF6 reveals the importance of oligomerization.定量比较 SARS 冠状病毒 ORF6 对核转运的抑制作用揭示了寡聚化的重要性。
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Insights into the role of Nup62 and Nup93 in assembling cytoplasmic ring and central transport channel of the nuclear pore complex.核孔复合体胞质环和中央运输通道组装中 Nup62 和 Nup93 作用的研究进展。
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Proteolytic Activities of Enterovirus 2A Do Not Depend on Its Interaction with SETD3.肠道病毒 2A 的蛋白水解活性不依赖于其与 SETD3 的相互作用。
Viruses. 2022 Jun 22;14(7):1360. doi: 10.3390/v14071360.
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Nucleocytoplasmic Trafficking Perturbation Induced by Picornaviruses.微小 RNA 干扰靶向 A 型流感病毒 NS1 基因抑制病毒复制及其对宿主细胞凋亡的影响
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The Role of Protein Disorder in Nuclear Transport and in Its Subversion by Viruses.蛋白质无序在核运输中的作用及其被病毒颠覆。
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Nuclear pore protein Nup98 is involved in replication of Rift Valley fever virus and nuclear import of virulence factor NSs.核孔蛋白 Nup98 参与裂谷热病毒的复制和毒力因子 NSs 的核输入。
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The Leader Protein of Theiler's Virus Prevents the Activation of PKR.西尼罗河病毒的主要结构蛋白可抑制 PKR 的激活。
J Virol. 2019 Sep 12;93(19). doi: 10.1128/JVI.01010-19. Print 2019 Oct 1.

本文引用的文献

1
Differential Disruption of Nucleocytoplasmic Trafficking Pathways by Rhinovirus 2A Proteases.鼻病毒2A蛋白酶对核质运输途径的差异性破坏
J Virol. 2017 Mar 29;91(8). doi: 10.1128/JVI.02472-16. Print 2017 Apr 15.
2
Solution structures of Mengovirus Leader protein, its phosphorylated derivatives, and in complex with nuclear transport regulatory protein, RanGTPase.脑心肌炎病毒前导蛋白、其磷酸化衍生物以及与核转运调节蛋白RanGTPase复合物的溶液结构
Proc Natl Acad Sci U S A. 2014 Nov 4;111(44):15792-7. doi: 10.1073/pnas.1411098111. Epub 2014 Oct 20.
3
Binding interactions between the encephalomyocarditis virus leader and protein 2A.脑心肌炎病毒前导序列与蛋白2A之间的结合相互作用。
J Virol. 2014 Nov;88(22):13503-9. doi: 10.1128/JVI.02148-14. Epub 2014 Sep 10.
4
AMP-activated protein kinase phosphorylates EMCV, TMEV and SafV leader proteins at different sites.AMP激活的蛋白激酶在不同位点使脑心肌炎病毒、Theiler小鼠脑脊髓炎病毒和萨菲病毒的前导蛋白磷酸化。
Virology. 2014 Aug;462-463:236-40. doi: 10.1016/j.virol.2014.06.026. Epub 2014 Jul 5.
5
Encephalomyocarditis virus leader is phosphorylated by CK2 and syk as a requirement for subsequent phosphorylation of cellular nucleoporins.脑心肌炎病毒前导序列被CK2和syk磷酸化，这是细胞核孔蛋白后续磷酸化的必要条件。
J Virol. 2014 Feb;88(4):2219-26. doi: 10.1128/JVI.03150-13. Epub 2013 Dec 11.
6
Viral subversion of the nuclear pore complex.病毒对核孔复合体的颠覆作用。
Viruses. 2013 Aug 16;5(8):2019-42. doi: 10.3390/v5082019.
7
Encephalomyocarditis virus Leader protein hinge domain is responsible for interactions with Ran GTPase.脑炎心肌炎病毒的 Leader 蛋白铰链结构域负责与 Ran GTPase 的相互作用。
Virology. 2013 Aug 15;443(1):177-85. doi: 10.1016/j.virol.2013.05.002. Epub 2013 May 25.
8
Guanine-nucleotide exchange factor RCC1 facilitates a tight binding between the encephalomyocarditis virus leader and cellular Ran GTPase.鸟嘌呤核苷酸交换因子 RCC1 促进脑心肌炎病毒的先导与细胞内 Ran GTP 酶的紧密结合。
J Virol. 2013 Jun;87(11):6517-20. doi: 10.1128/JVI.02493-12. Epub 2013 Mar 27.
9
Differential processing of nuclear pore complex proteins by rhinovirus 2A proteases from different species and serotypes.不同种属和血清型鼻病毒 2A 蛋白酶对核孔复合体蛋白的差异加工。
J Virol. 2011 Oct;85(20):10874-83. doi: 10.1128/JVI.00718-11. Epub 2011 Aug 10.
10
Nucleoporin phosphorylation triggered by the encephalomyocarditis virus leader protein is mediated by mitogen-activated protein kinases.脑炎心肌炎病毒衣壳蛋白触发的核孔蛋白磷酸化是由丝裂原活化蛋白激酶介导的。
J Virol. 2010 Dec;84(24):12538-48. doi: 10.1128/JVI.01484-09. Epub 2010 Sep 29.

三种心病毒前导蛋白同等程度地抑制四种不同的核质运输途径。

Three cardiovirus Leader proteins equivalently inhibit four different nucleocytoplasmic trafficking pathways.

作者信息

Ciomperlik Jessica J, Basta Holly A, Palmenberg Ann C

机构信息

Institute for Molecular Virology, and Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, United States.

Department of Biology, Rocky Mountain College, Billings, MT, United States.

出版信息

Virology. 2015 Oct;484:194-202. doi: 10.1016/j.virol.2015.06.004. Epub 2015 Jun 23.

DOI:10.1016/j.virol.2015.06.004
PMID:26115166
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4567469/
Abstract

Cardiovirus infections inhibit nucleocytoplasmic trafficking by Leader protein-induced phosphorylation of Phe/Gly-containing nucleoporins (Nups). Recombinant Leader from encephalomyocarditis virus, Theiler׳s murine encephalomyelitis virus and Saffold virus target the same subset of Nups, including Nup62 and Nup98, but not Nup50. Reporter cell lines with fluorescence mCherry markers for M9, RS and classical SV40 import pathways, as well as the Crm1-mediated export pathway, all responded to transfection with the full panel of Leader proteins, showing consequent cessation of path-specific active import/export. For this to happen, the Nups had to be presented in the context of intact nuclear pores and exposed to cytoplasmic extracts. The Leader phosphorylation cascade was not effective against recombinant Nup proteins. The findings support a model of Leader-dependent Nup phosphorylation with the purpose of disrupting Nup-transportin interactions.

摘要

心病毒感染通过前导蛋白诱导含苯丙氨酸/甘氨酸的核孔蛋白（Nups）磷酸化来抑制核质运输。来自脑心肌炎病毒、泰勒氏鼠脑脊髓炎病毒和萨福尔德病毒的重组前导蛋白靶向相同的核孔蛋白亚群，包括Nup62和Nup98，但不包括Nup50。具有用于M9、RS和经典SV40导入途径以及Crm1介导的输出途径的荧光mCherry标记的报告细胞系，对用全套前导蛋白进行转染均有反应，显示出相应的特定途径的主动导入/输出停止。要发生这种情况，核孔蛋白必须处于完整核孔的环境中并暴露于细胞质提取物中。前导蛋白磷酸化级联反应对重组核孔蛋白无效。这些发现支持了一种依赖前导蛋白的核孔蛋白磷酸化模型，其目的是破坏核孔蛋白-转运蛋白相互作用。