HUMAN CYTOMEGALOVIRUS INHIBITS CELLULAR DNA-SYNTHESIS AND ARRESTS PRODUCTIVELY INFECTED-CELLS IN LATE G1

Human embryonic lung fibroblasts (LU) can be productively infected wit h human cytomegalovirus (HCMV). During the course of productive infect ion, the virus elicits a number of responses that resemble certain asp ects of G1 cell cycle progression. The virus activates cyclin E/Cdk2 k inase in both subconfluent, serum-arrested, and density-arrested cultu res. Activation of cyclin 5-dependent kinase is due, in part, to induc tion of cyclin E and, in part, to inhibition of the cyclin kinase inhi bitors, Cip1 and Kip1. However, G1 progression is incomplete in HCMV-i nfected cells. Neither cyclin A nor cyclin D is induced, and cellular DNA synthesis does not occur if one takes care to avoid addition of fr esh serum to serum-starved cultures. The data indicate that the virus induces a state of late G1 arrest, in which cyclin E/Cdk2 activates nu cleotide metabolism and other biosynthetic processes that are necessar y for viral replication. Failure to activate host cell DNA synthesis e nsures that the virus will have uncompeted access to such precursors. (C) 1996 Academic Press, Inc.