Cytomegalovirus infection induces high levels of cyclins, phosphorylated Rb, and p53, leading to cell cycle arrest

F M Jault; J M Jault; F Ruchti; E A Fortunato; C Clark; J Corbeil; D D Richman; D H Spector

doi:10.1128/JVI.69.11.6697-6704.1995

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Cytomegalovirus infection induces high levels of cyclins, phosphorylated Rb, and p53, leading to cell cycle arrest

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Cytomegalovirus infection induces high levels of cyclins, phosphorylated Rb, and p53, leading to cell cycle arrest

F M Jault, J M Jault, F Ruchti, E A Fortunato, C Clark, J Corbeil, D D Richman and D H Spector

Journal of virology, Vol.69(11), pp.6697-6704

11/1995

DOI: https://doi.org/10.1128/JVI.69.11.6697-6704.1995

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https://hdl.handle.net/2376/107255

PMCID: PMC189579

PMID: 7474079

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https://doi.org/10.1128/JVI.69.11.6697-6704.1995View

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Abstract

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.

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Title: Cytomegalovirus infection induces high levels of cyclins, phosphorylated Rb, and p53, leading to cell cycle arrest
Creators: F M Jault - Department of Biology, University of California, San Diego, La Jolla 92093-0357, USA
J M Jault - Department of Biology, University of California, San Diego, La Jolla 92093-0357, USA
F Ruchti - Department of Biology, University of California, San Diego, La Jolla 92093-0357, USA
E A Fortunato - Department of Biology, University of California, San Diego, La Jolla 92093-0357, USA
C Clark - Department of Biology, University of California, San Diego, La Jolla 92093-0357, USA
J Corbeil - Department of Biology, University of California, San Diego, La Jolla 92093-0357, USA
D D Richman - Department of Biology, University of California, San Diego, La Jolla 92093-0357, USA
D H Spector - Department of Biology, University of California, San Diego, La Jolla 92093-0357, USA
Publication Details: Journal of virology, Vol.69(11), pp.6697-6704
Academic Unit: UNKNOWN
Identifiers: 99900547090201842
Language: English
Resource Type: Journal article