Role of human cytomegalovirus immediate-early proteins in cell growth control
UMass Chan Affiliations
Department of Molecular Genetics and MicrobiologyGraduate School of Biomedical Sciences
Document Type
Journal ArticlePublication Date
2000-08-10Keywords
Adenoviridae; Animals; Blotting, Western; Cell Cycle; Cell Division; Cell Line; Cytomegalovirus; Embryo, Mammalian; Fibroblasts; Flow Cytometry; Humans; Immediate-Early Proteins; *Membrane Glycoproteins; Rats; *Trans-Activators; Tumor Suppressor Protein p53; *Viral Envelope Proteins; *Viral ProteinsLife Sciences
Medicine and Health Sciences
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Show full item recordAbstract
Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus that has been implicated in several disorders, including an association between HCMV reactivation and the overproliferation of arterial smooth muscle cells observed in restenosis. Although HCMV can mediate a growth-arrest phenotype in infected cells, the virus can also promote an environment conducive to proliferation. Here, we present evidence that the HCMV immediate-early (IE) proteins, IE1-72 and IE2-86, may be responsible for inducing this proliferative environment by altering cell cycle control. We find that expression of either of these IE proteins can alter the cell cycle distribution of randomly cycling cells towards S and G(2)/M phases. Additionally, we find that expression of IE2-86, but not IE1-72, induces quiescent cells into S phase and delays cell cycle exit. In the absence of p53, IE1-72 expression can induce S phase and delay cell cycle exit. We also demonstrate that p53 protein levels increase in fibroblasts following the expression of IE1-72. The observed accumulation of p53 protein in IE1-72-expressing cells may account for the inability of IE1-72 to induce S phase and delay cell cycle exit. Our data suggest that expression of HCMV IE1-72 and IE2-86 is sufficient to alter the cell cycle to generate an environment conducive to proliferation.Source
J Virol. 2000 Sep;74(17):8028-37.
DOI
10.1128/JVI.74.17.8028-8037.2000Permanent Link to this Item
http://hdl.handle.net/20.500.14038/33394PubMed ID
10933712Related Resources
ae974a485f413a2113503eed53cd6c53
10.1128/JVI.74.17.8028-8037.2000
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