Influenza A Virus Replication Induces Cell Cycle Arrest in G0/G1 Phase
Influenza A Virus Replication Induces Cell Cycle Arrest in G0/G1 Phase
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DOI：
10.1128/jvi.01216-10
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发表时间：
2010-12-01
影响因子：
5.4
通讯作者：
Sun, Bing
中科院分区：
文献类型：
--
作者：
He, Yuan;Xu, Ke;Sun, Bing
许多病毒与宿主细胞分裂周期相互作用以促进其自身生长。在这项研究中，我们研究了甲型流感病毒操纵细胞周期进程的能力。我们的研究结果表明，甲型流感病毒A/WSN/33（H1N1）复制导致感染细胞的G（0）/G（1）期积累，这种积累是由阻止细胞周期从G（0）/G（1）期进入S期引起的。与G（0）/G（1）期积累一致，高度磷酸化的视网膜母细胞瘤蛋白的量在A/WSN/33（H1N1）病毒感染后减少，所述高度磷酸化的视网膜母细胞瘤蛋白是细胞周期通过晚期G（1）进入S期的必要活性形式。此外，细胞周期调控中的其他关键分子，如p21、cyclin E和cyclin D1也发生了变化，并显示出G（0）/G（1）期细胞周期停滞的模式。有趣的是，与未同步化的细胞或在G（2）/M期同步化的细胞相比，在G（0）/G（1）期同步化的细胞中观察到增加的病毒蛋白表达和子代病毒产生。G（0）/G（1）期细胞周期停滞可能是一种常见的策略，因为在其他毒株中也观察到了这种效果，如H3 N2、H9 N2、PR 8 H1N1和大流行性猪H1N1病毒。总之，这些发现表明，甲型流感病毒可能通过诱导感染细胞的G（0）/G（1）期细胞周期停滞，为病毒蛋白积累和病毒生产提供有利条件。
Many viruses interact with the host cell division cycle to favor their own growth. In this study, we examined the ability of influenza A virus to manipulate cell cycle progression. Our results show that influenza A virus A/WSN/33 ( H1N1) replication results in G(0)/G(1)-phase accumulation of infected cells and that this accumulation is caused by the prevention of cell cycle entry from G(0)/G(1) phase into S phase. Consistent with the G(0)/G(1)-phase accumulation, the amount of hyperphosphorylated retinoblastoma protein, a necessary active form for cell cycle progression through late G(1) into S phase, decreased after infection with A/WSN/33 ( H1N1) virus. In addition, other key molecules in the regulation of the cell cycle, such as p21, cyclin E, and cyclin D1, were also changed and showed a pattern of G(0)/G(1)-phase cell cycle arrest. It is interesting that increased viral protein expression and progeny virus production in cells synchronized in the G(0)/G(1) phase were observed compared to those in either unsynchronized cells or cells synchronized in the G(2)/M phase. G(0)/G(1)-phase cell cycle arrest is likely a common strategy, since the effect was also observed in other strains, such as H3N2, H9N2, PR8 H1N1, and pandemic swine H1N1 viruses. These findings, in all, suggest that influenza A virus may provide favorable conditions for viral protein accumulation and virus production by inducing a G(0)/G(1)-phase cell cycle arrest in infected cells.