Murine coronavirus replication induces cell cycle arrest in G0/G1 phase
Murine coronavirus replication induces cell cycle arrest in G0/G1 phase
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DOI：
10.1128/jvi.78.11.5658-5669.2004
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发表时间：
2004-06-01
影响因子：
5.4
通讯作者：
Makino, S
中科院分区：
文献类型：
--
作者：
Chen, CJ;Makino, S
小鼠肝炎病毒 (MHV) 在活跃生长的 DBT 和 17CI-1 细胞中复制，导致宿主细胞 DNA 合成受到抑制，感染细胞在细胞周期的 G、G、期积累。紫外线照射的 MHV 未能抑制宿主细胞 DNA 的合成。通过血清剥夺使静态17CI-1细胞同步进入G期的MHV感染阻止了受感染细胞在血清刺激后进入S期。 MHV 复制抑制视网膜母细胞瘤蛋白 (pRb) 的过度磷酸化，这是细胞周期进展到 G 晚期并进入 S 期所必需的事件。虽然受感染细胞中细胞周期蛋白依赖性激酶 (Cdk) 抑制剂 p21(Cip1)、p27(Kip1) 和 p16(INK4a) 的量没有变化，但异步培养物中的 MHV 感染诱导 DBT 和 17CI-1 细胞和 17CI-1 细胞中 Cdk6 水平降低。感染还导致两种细胞系中 Cdk2 活性下降。静息 17CI-1 细胞中的 MHV 感染可阻止血清刺激后 Cdk4、Cdk6、细胞周期蛋白 D1 和细胞周期蛋白 D3 水平的正常增加。在模拟感染的细胞中，血清刺激后，细胞周期蛋白D2和细胞周期蛋白E的含量没有显着增加，而在MHV感染的细胞中，细胞周期蛋白D2和细胞周期蛋白E的含量却减少，这表明MHV感染可能诱导细胞周期蛋白D2和细胞周期蛋白E降解。我们的数据表明，MHV 感染细胞中 G(1) 细胞周期蛋白-Cdk 复合物数量的减少导致 Cdk 活性降低和 pRb 过度磷酸化不足，从而抑制细胞周期在 G(0)/G(1) 期。
Mouse hepatitis virus (MHV) replication in actively growing DBT and 17CI-1 cells resulted in the inhibition of host cellular DNA synthesis and the accumulation of infected cells in the G, G, phase of the cell cycle. UV-irradiated MHV failed to inhibit host cellular DNA synthesis. MHV infection in quiescent 17CI-1 cells that had been synchronized in the G, phase by serum deprivation prevented infected cells from entering the S phase after serum stimulation. MHV replication inhibited hyperphosphorylation of the retinoblastoma protein (pRb), the event that is necessary for cell cycle progression through late G, and into the S phase. While the amounts of the cellular cyclin-dependent kinase (Cdk) inhibitors p21(Cip1), p27(Kip1), and p16(INK4a) did not change in infected cells, MHV infection in asynchronous cultures induced a clear reduction in the amounts of Cdk4 and G(1) cyclins (cyclins D1, D2, D3, and E) in both DBT and 17CI-1 cells and a reduction in Cdk6 levels in 17CI-1 cells. Infection also resulted in a decrease in Cdk2 activity in both cell lines. MHV infection in quiescent 17CI-1 cells prevented normal increases in Cdk4, Cdk6, cyclin D1, and cyclin D3 levels after serum stimulation. The amounts of cyclin D2 and cyclin E were not increased signiticantly after serum stimulation in mock-infected cells, whereas they were decreased in MHV-infected cells, suggesting the possibility that MHV infection may induce cyclin D2 and cyclin E degradation. Our data suggested that a reduction in the amounts of G(1) cyclin-Cdk complexes in MHV-infected cells led to a reduction in Cdk activities and insufficient hyperphosphorylation of pRb, resulting in inhibition of the cell cycle in the G(0)/G(1) phase.