Perturbation of cell cycle progression and cellular gene expression as a function of herpes simplex virus ICP0
Perturbation of cell cycle progression and cellular gene expression as a function of herpes simplex virus ICP0
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DOI：
10.1128/jvi.73.10.8245-8255.1999
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发表时间：
1999-10-01
影响因子：
5.4
通讯作者：
DeLuca, NA
中科院分区：
文献类型：
--
作者：
Hobbs, WE;DeLuca, NA
单纯疱疹病毒1型能够在裂解感染后抑制宿主细胞DNA合成。然而，尚未描述对细胞周期进程的潜在影响的机制和性质。在这份报告中，我们的特点与复制缺陷病毒d106，其中立即早期基因表达被限制在感染细胞多肽0（ICP 0）和所有其他病毒基因的表达感染后的细胞周期失调是显着减少或未观察到。d106感染导致细胞在G（1）/S和G（2）/M区室中积聚，与两个检查点的细胞周期阻滞一致。不表达任何病毒蛋白的同基因变体d109未能诱导这种表型，表明ICP 0的表达对细胞周期停滞至关重要。用d106和d109感染后的全球细胞基因表达模式的分析显示，作为ICP 0表达的结果，诱导了相对较小的细胞基因子集。在ICP 0存在下诱导的许多这些基因被经典地认为是p53应答基因，包括p21、gadd 45和mdm-2。然而，感染d106的细胞与两个等位基因的p53删除导致相同的细胞周期阻滞表型和相似的细胞基因表达模式，表明ICP 0的表达可能通过p53依赖性和p53非依赖性机制导致细胞周期阻滞。此外，发现用d106感染对病毒和细胞基因表达的影响与用组蛋白脱乙酰酶抑制剂阿司他丁A处理细胞后观察到的影响相似。
Herpes simplex virus type 1 is capable of inhibiting host cell DNA synthesis following lytic infection. However, the mechanism and nature of potential effects on cell cycle progression have not been described. In this report, we characterize the dysregulation of the cell cycle following infection with the replication-incompetent virus d106, where immediate-early gene expression is restricted to infected-cell polypeptide 0 (ICP0) and the expression of all other viral genes is dramatically reduced or is not observed. Infection with d106 resulted in the accumulation of cells in both the G(1)/S and G(2)/M compartments, consistent with cell cycle arrest at both checkpoints. The isogenic variant d109, which does not express any viral proteins, failed to induce this phenotype, suggesting that the expression of ICP0 is crucial for cell cycle arrest. Analysis of global cellular gene expression patterns following infection with d106 and d109 revealed that a relatively small subset of cellular genes were induced as a consequence of ICP0 expression. A number of these genes induced in the presence of ICP0 are classically considered p53-responsive genes, including p21, gadd45, and mdm-2. However, infection with d106 of cells with both alleles of p53 deleted resulted in the same cell cycle arrest phenotype and similar cellular gene expression patterns, suggesting that the expression of ICP0 results in cell cycle arrest potentially via p53-dependent and p53-independent mechanisms. In addition, it was found that the effects of infection with d106 on viral and cellular gene expression were similar to the effects observed following treatment of cells with the histone deacetylase inhibitor trichostatin A.