Vaccinia Virus Arrests and Shifts the Cell Cycle.

Vaccinia Virus Arrests and Shifts the Cell Cycle.
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DOI:
10.3390/v14020431
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发表时间:
2022-02-19
期刊:
Viruses
影响因子:
--
通讯作者:
Mercer J
Mercer J
中科院分区:
其他
文献类型:
--
作者:
Martin CK;Samolej J;Olson AT;Bertoli C;Wiebe MS;de Bruin RAM;Mercer J

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调节宿主细胞周期是病毒用来创造促复制环境的一种常用策略。据报道,为了促进病毒基因组复制,牛痘病毒(VACV)可以改变细胞周期调节并触发宿主细胞DNA损伤反应。然而,介导这些变化的细胞因子和病毒效应物仍然未知。在这里,我们着手研究VACV感染对细胞增殖和宿主细胞周期进程的影响。利用VACV突变体的一个子集,我们描述了抑制细胞增殖所需的感染阶段,并定义了调节宿主细胞周期所需的病毒效应物。与先前的研究一致,我们表明VACV抑制并随后改变宿主细胞周期。我们证明这两种现象是相互独立的,病毒早期基因负责细胞周期抑制,而复制后病毒基因负责细胞周期转移。扩展先前的研究结果,我们发现病毒激酶F10是激活DNA损伤检查点所必需的,病毒B1激酶和/或B12假激酶在感染期间介导检查点效应物p53和p21的降解。我们得出结论,VACV通过多种VACV效应蛋白的时间表达调节宿主细胞增殖和宿主细胞周期进程。(209/200)。
Modulation of the host cell cycle is a common strategy used by viruses to create a pro-replicative environment. To facilitate viral genome replication, vaccinia virus (VACV) has been reported to alter cell cycle regulation and trigger the host cell DNA damage response. However, the cellular factors and viral effectors that mediate these changes remain unknown. Here, we set out to investigate the effect of VACV infection on cell proliferation and host cell cycle progression. Using a subset of VACV mutants, we characterise the stage of infection required for inhibition of cell proliferation and define the viral effectors required to dysregulate the host cell cycle. Consistent with previous studies, we show that VACV inhibits and subsequently shifts the host cell cycle. We demonstrate that these two phenomena are independent of one another, with viral early genes being responsible for cell cycle inhibition, and post-replicative viral gene(s) responsible for the cell cycle shift. Extending previous findings, we show that the viral kinase F10 is required to activate the DNA damage checkpoint and that the viral B1 kinase and/or B12 pseudokinase mediate degradation of checkpoint effectors p53 and p21 during infection. We conclude that VACV modulates host cell proliferation and host cell cycle progression through temporal expression of multiple VACV effector proteins. (209/200.)
DOI: 10.1007/978-1-4939-0888-2_10
发表时间: 2014
期刊: Methods in molecular biology (Clifton, N.J.)
影响因子: --
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影响因子: 9.8
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发表时间: 1980-01-01
期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子: --
作者:
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通讯作者: SPRINGER, J
DOI: 10.1126/science.282.5393.1497
发表时间: 1998-11-20
期刊: SCIENCE
影响因子: 56.9
作者:
Bunz, F;Dutriaux, A;Vogelstein, B
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DOI: 10.4161/cc.6364
发表时间: 2008-08-01
期刊: CELL CYCLE
影响因子: 4.3
作者:
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通讯作者: Keyomarsi, Khandan