Human embryonic lung fibroblasts (LU) can be productively infected h 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 uncompeted access to such precursors.
Bibliographical noteFunding Information:
This work was supported in part by NIH Grants DE11389 and ES06676 and EPA Grant R81-9495 to T.A. and NIH Grants AG10514 and CA24347 to E.A.T. W.A.B. is a recipient of a James W. McLaughlin Predoctoral Fellowship.