Human cytomegalovirus inhibits cellular DNA synthesis and arrests productively infected cells in late G1
Human cytomegalovirus inhibits cellular DNA synthesis and arrests productively infected cells in late G1
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DOI：
10.1006/viro.1996.0516
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发表时间：
1996-10-01
期刊：
影响因子：
3.7
通讯作者：
Albrecht, T
中科院分区：
文献类型：
--
作者：
Bresnahan, WA;Boldogh, I;Albrecht, T
人巨细胞病毒（HCMV）能高效感染人胚肺成纤维细胞（LU）。在生产性感染的过程中，病毒激发了许多类似于G1细胞周期进展的某些方面的反应。病毒激活细胞周期蛋白E/Cdk 2激酶在两个亚融合，血清逮捕，和密度逮捕的文化。细胞周期蛋白5依赖性激酶的激活部分是由于细胞周期蛋白E的诱导，部分是由于细胞周期蛋白激酶抑制剂Cip 1和Kip 1的抑制。然而，在HCMV感染的细胞中，G1进展是不完全的。细胞周期蛋白A和细胞周期蛋白D都不会被诱导，如果注意避免向血清饥饿培养物中加入新鲜血清，细胞DNA合成也不会发生。这些数据表明，该病毒诱导晚期G1停滞状态，其中细胞周期蛋白E/Cdk 2激活核苷酸代谢和病毒复制所必需的其他生物合成过程。不能激活宿主细胞DNA合成确保了病毒将无竞争地接近这些前体。(C)出版社：Academic Press，Inc.
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 5-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 uncompeted access to such precursors. (C) 1996 Academic Press, Inc.