Cell cycle perturbations induced by infection with the coronavirus infectious bronchitis virus and their effect on virus replication

Cell cycle perturbations induced by infection with the coronavirus infectious bronchitis virus and their effect on virus replication
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DOI:
10.1128/jvi.80.8.4147-4156.2006
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发表时间:
2006-04-01
影响因子:
5.4
通讯作者:
Hiscox, JA
Hiscox, JA
中科院分区:
医学2区
文献类型:
--
作者:
Dove, B;Brooks, G;Hiscox, JA

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在真核细胞中,细胞生长和分裂以一种被称为细胞周期的过程所描述的逐步有序的方式发生。正链RNA病毒与细胞周期的关系及其对病毒复制的影响尚不清楚。我们已经证明,用禽冠状病毒传染性支气管炎病毒(IBV)(一种正链RNA病毒)感染异步复制和同步复制的细胞,会导致感染细胞在细胞周期的G(2)/M期积累。对各种细胞周期调节蛋白和细胞形态的分析表明,细胞周期蛋白D1和D2 (G(2)调节细胞周期蛋白)下调,并且一部分病毒感染的细胞发生了异常的细胞质分裂,细胞发生了核分裂,而不是细胞质分裂。我们评估了扰动对病毒感染细胞的细胞周期的影响,发现ibv感染的G(2)/ m期同步细胞与Go期同步细胞或异步复制细胞相比,从阻滞中释放时病毒蛋白产量增加。我们的数据表明,IBV在感染细胞中诱导G(2)/M期阻滞,为病毒复制创造有利条件。
In eukaryotic cells, cell growth and division occur in a stepwise, orderly fashion described by a process known as the cell cycle. The relationship between positive-strand RNA viruses and the cell cycle and the concomitant effects on virus replication are not clearly understood. We have shown that infection of asynchronously replicating and synchronized replicating cells with the avian coronavirus infectious bronchitis virus (IBV), a positive-strand RNA virus, resulted in the accumulation of infected cells in the G(2)/M phase of the cell cycle. Analysis of various cell cycle-regulatory proteins and cellular morphology indicated that there was a down-regulation of cyclins D1 and D2 (G(2) regulatory cyclins) and that a proportion of virus-infected cells underwent aberrant cytokinesis, in which the cells underwent nuclear, but not cytoplasmic, division. We assessed the impact of the perturbations on the cell cycle for virus-infected cells and found that IBV-infected G(2)/M-phase-synchronized cells exhibited increased viral protein production when released from the block when compared to cells synchronized in the Go phase or asynchronously replicating cells. Our data suggested that IBV induces a G(2)/M phase arrest in infected cells to promote favorable conditions for viral replication.