Human cytomegalovirus inhibits cellular DNA synthesis and arrests productively infected cells in late G1.
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.
Bresnahan
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WA
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston 77555, USA.
Boldogh
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I
Thompson
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EA
Albrecht
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T
D042846:CDC2-CDC28 Kinases; D002460:Cell Line; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D003587:Cytomegalovirus / Q000235:genetics / Q000502:physiology*; D004247:DNA / Q000096:biosynthesis*; D004279:DNA, Viral / Q000096:biosynthesis; D004789:Enzyme Activation; D016193:G1 Phase; D015870:Gene Expression; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism
D016213:Cyclins; D004279:DNA, Viral; D004247:DNA; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases