Bresnahan W A, Boldogh I, Thompson E A, Albrecht T
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston 77555, USA.
Virology. 1996 Oct 1;224(1):150-60. doi: 10.1006/viro.1996.0516.
Human embryonic lung fibroblasts (LU) can be productively infected with human cytomegalovirus (HCMV). During the course of productive infection, the virus elicits a number of responses that resemble certain aspects of G1 cell cycle progression. The virus activates cyclin E/Cdk2 kinase in both subconfluent, serum-arrested, and density-arrested cultures. Activation of cyclin E-dependent kinase is due, in part, to induction of cyclin E and, in part, to inhibition of the cyclin kinase inhibitors, Cip1 and Kip1. However, G1 progression is incomplete in HCMV-infected cells. Neither cyclin A nor cyclin D is induced, and cellular DNA synthesis does not occur if one takes care to avoid addition of fresh serum to serum-starved cultures. The data indicate that the virus induces a state of late G1 arrest, in which cyclin E/Cdk2 activates nucleotide metabolism and other biosynthetic processes that are necessary for viral replication. Failure to activate host cell DNA synthesis ensures that the virus will have uncompleted access to such precursors.
人胚肺成纤维细胞（LU）可被人巨细胞病毒（HCMV）有效感染。在有效感染过程中，该病毒引发了许多类似于G1期细胞周期进程某些方面的反应。在亚汇合、血清阻滞和密度阻滞培养物中，病毒均可激活细胞周期蛋白E/细胞周期蛋白依赖性激酶2（Cdk2）激酶。细胞周期蛋白E依赖性激酶的激活部分归因于细胞周期蛋白E的诱导，部分归因于细胞周期蛋白激酶抑制剂Cip1和Kip1的抑制。然而，在HCMV感染的细胞中，G1期进程并不完整。细胞周期蛋白A和细胞周期蛋白D均未被诱导，并且如果注意避免向血清饥饿培养物中添加新鲜血清，则不会发生细胞DNA合成。数据表明，该病毒诱导了一种晚期G1期阻滞状态，其中细胞周期蛋白E/Cdk2激活核苷酸代谢和病毒复制所需的其他生物合成过程。未能激活宿主细胞DNA合成可确保病毒无法完全获取此类前体物质。
