PMID- 7474079 OWN - NLM STAT- MEDLINE DCOM- 19951201 LR - 20211008 IS - 0022-538X (Print) IS - 1098-5514 (Electronic) IS - 0022-538X (Linking) VI - 69 IP - 11 DP - 1995 Nov TI - Cytomegalovirus infection induces high levels of cyclins, phosphorylated Rb, and p53, leading to cell cycle arrest. PG - 6697-704 AB - Human cytomegalovirus (HCMV) infection stimulates cellular DNA synthesis and causes chromosomal damage. Because such events likely affect cellular proliferation, we investigated the impact of HCMV infection on key components of the cell cycle. Early after infection, HCMV induced elevated levels of cyclin E, cyclin E-associated kinase activity, and two tumor suppressor proteins, p53 and the retinoblastoma gene product (Rb). The steady-state concentration of Rb continued to rise throughout the infection, with most of the protein remaining in the highly phosphorylated form. At early times, HCMV infection also induced cyclin B accumulation, which was associated with a significant increase in mitosis-promoting factor activity as the infection progresses. In contrast, the levels of cyclin A and cyclin A-associated kinase activity increased only at late times in the infection, and the kinetics were delayed relative to those for cyclins E and B. Analysis of the cellular DNA content in the infected cells by flow cytometry showed a progressive shift of the cells from the G1 to the S and G2/M phases of the cell cycle, leading to an accumulation of aneuploid cells at late times. We propose that these HCMV-mediated perturbations result in cell cycle arrest in G2/M. FAU - Jault, F M AU - Jault FM AD - Department of Biology, University of California, San Diego, La Jolla 92093-0357, USA. FAU - Jault, J M AU - Jault JM FAU - Ruchti, F AU - Ruchti F FAU - Fortunato, E A AU - Fortunato EA FAU - Clark, C AU - Clark C FAU - Corbeil, J AU - Corbeil J FAU - Richman, D D AU - Richman DD FAU - Spector, D H AU - Spector DH LA - eng GR - AI27670/AI/NIAID NIH HHS/United States GR - AI36214/AI/NIAID NIH HHS/United States GR - CA34729/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (Cyclins) RN - 0 (Retinoblastoma Protein) RN - 0 (Tumor Suppressor Protein p53) SB - IM MH - *Cell Cycle MH - Cell Division MH - *Cell Transformation, Viral MH - Cells, Cultured MH - Cyclins/*biosynthesis MH - Cytomegalovirus/genetics/*physiology MH - DNA Replication MH - Fibroblasts/cytology MH - Humans MH - Kinetics MH - Male MH - Phosphorylation MH - Retinoblastoma Protein/*metabolism MH - Skin/cytology MH - Time Factors MH - Tumor Suppressor Protein p53/*metabolism PMC - PMC189579 EDAT- 1995/11/01 00:00 MHDA- 1995/11/01 00:01 PMCR- 1995/11/01 CRDT- 1995/11/01 00:00 PHST- 1995/11/01 00:00 [pubmed] PHST- 1995/11/01 00:01 [medline] PHST- 1995/11/01 00:00 [entrez] PHST- 1995/11/01 00:00 [pmc-release] AID - 10.1128/JVI.69.11.6697-6704.1995 [doi] PST - ppublish SO - J Virol. 1995 Nov;69(11):6697-704. doi: 10.1128/JVI.69.11.6697-6704.1995.