Extended stability of cyclin D1 contributes to limited cell cycle arrest at G1-phase in BHK-21 cells with Japanese encephalitis virus persistent infection.
Extended stability of cyclin D1 contributes to limited cell cycle arrest at G1-phase in BHK-21 cells with Japanese encephalitis virus persistent infection.
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细胞周期蛋白D1的稳定性促进了日本脑炎病毒持续感染的BHK-21细胞中G1相的细胞周期停滞有限。
DOI：
10.1007/s12275-015-4661-z
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发表时间：
2015-01
期刊：
影响因子：
--
通讯作者：
Jeong YS
中科院分区：
文献类型：
--
作者：
Kim JY;Park SY;Lyoo HR;Koo ES;Kim MS;Jeong YS
越来越多的证据表明，许多 RNA 病毒操纵细胞周期控制，以获得有利于其在感染期间有效复制的细胞环境。尽管病毒诱导的 G0/G1 停滞通常会暂时延迟早期细胞凋亡，但受感染病毒的长时间复制会导致宿主细胞最终死亡。相比之下，大多数受到RNA病毒持续感染的哺乳动物细胞在存在高效病毒复制的情况下通常会逃避细胞溶解。在这项研究中，我们证明了细胞周期蛋白 D1 的延长耐受性与持续感染日本脑炎病毒 (JEV) 的 BHK-21 细胞中糖原合酶激酶-3ß (GSK-3ß) 表达的抑制明显相关。与 JEV 急性感染的正常 BHK-21 细胞相比，这些细胞的 G0/G1 停滞变得更加松弛。放线菌酮处理后，持续感染细胞中的细胞周期蛋白D1比急性感染细胞中的细胞周期蛋白D1持续时间长几个小时。此外，细胞核内细胞周期蛋白D1积累的正调节因子p21Cip1和p27Kip1的表达均受到抑制，这与JEV急性感染时的情况形成鲜明对比。在 JEV 急性感染中，通过氯化锂治疗抑制 GSK-3ß 可挽救大量细胞免于细胞溶解，这与从蛋白水解中逃脱的细胞周期蛋白 D1 水平一致。因此，JEV持续感染的BHK-21细胞中G1/S停滞的限制与GSK-3ß表达的抑制有关，导致细胞周期蛋白D1的持续时间延长。
There is increasing evidence that many RNA viruses manipulate cell cycle control to achieve favorable cellular environments for their efficient replication during infection. Although virus-induced G0/G1 arrest often delays early apoptosis temporarily, a prolonged replication of the infected virus leads host cells to eventual death. In contrast, most mammalian cells with RNA virus persistent infection often escape cytolysis in the presence of productive viral replication. In this study, we demonstrated that the extended endurance of cyclin D1 was clearly associated with the suppression of glycogen synthase kinase-3ß (GSK-3ß) expression in BHK-21 cells that are persistently infected with Japanese encephalitis virus (JEV). The G0/G1 arrest of these cells turned much loose compared to the normal BHK-21 cells with JEV acute infection. After cycloheximide treatment, cyclin D1 in the persistently infected cells lasted several hours longer than those in acutely infected cells. Furthermore, both p21Cip1 and p27Kip1, positive regulators for cyclin D1 accumulation in the nucleus, were suppressed in their expression, which contrasts with those in JEV acute infection. Inhibition of the GSK-3ß by lithium chloride treatment rescued a significant number of cells from cytolysis in JEV acute infection, which coincided with the levels of cyclin D1 that escaped from proteolysis. Therefore, the limitation of G1/S arrest in the BHK-21 cells with JEV persistent infection is associated with the suppression of GSK-3ß expression, resulting in the extended duration of cyclin D1.
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