| Cell cycle-independent expression of immediate-early gene 3 results in G1 and G2 arrest in murine cytomegalovirus-infected cells. | |
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MedLine Citation:
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PMID: 18667506 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The infectious cycle of human cytomegalovirus (HCMV) is intricately linked to the host's cell cycle. Viral gene expression can be initiated only in G(0)/G(1) phase. Once expressed, the immediate-early gene product IE2 prevents cellular DNA synthesis, arresting infected cells with a G(1) DNA content. This function is required for efficient viral replication in vitro. A prerequisite for addressing its in vivo relevance is the characterization of cell cycle-regulatory activities of CMV species for which animal models have been established. Here, we show that murine CMV (MCMV), like HCMV, has a strong antiproliferative capacity and arrests cells in G(1). Unexpectedly, and in contrast to HCMV, MCMV can also block cells that have passed through S phase by arresting them in G(2). Moreover, MCMV can also replicate in G(2) cells. This is made possible by the cell cycle-independent expression of MCMV immediate-early genes. Transfection experiments show that of several MCMV candidate genes, only immediate-early gene 3 (ie3), the homologue of HCMV IE2, exhibits cell cycle arrest activity. Accordingly, an MCMV ie3 deletion mutant has lost the ability to arrest cells in either G(1) or G(2). Thus, despite interspecies variations in the cell cycle dependence of viral gene expression, the central theme of HCMV IE2-induced cell cycle arrest is conserved in the murine counterpart, raising the possibility of studying its physiological relevance at the level of the whole organism. |
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Authors:
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Lüder Wiebusch; Anke Neuwirth; Linus Grabenhenrich; Sebastian Voigt; Christian Hagemeier |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-07-30 |
Journal Detail:
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Title: Journal of virology Volume: 82 ISSN: 1098-5514 ISO Abbreviation: J. Virol. Publication Date: 2008 Oct |
Date Detail:
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Created Date: 2008-09-30 Completed Date: 2008-10-14 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 0113724 Medline TA: J Virol Country: United States |
Other Details:
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Languages: eng Pagination: 10188-98 Citation Subset: IM |
Affiliation:
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Department of Pediatrics, Laboratory for Molecular Biology, Charité-Universitätsmedizin Berlin, Ziegelstr. 5-9, 10117 Berlin, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Proliferation DNA Replication G1 Phase / physiology* G2 Phase / physiology* Gene Expression Regulation, Viral* Genes, Immediate-Early / genetics* Humans Immediate-Early Proteins / genetics, metabolism Mice Muromegalovirus / genetics*, pathogenicity, physiology* NIH 3T3 Cells Trans-Activators / genetics, metabolism |
| Chemical | |
Reg. No./Substance:
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0/IE2 protein, Cytomegalovirus; 0/Immediate-Early Proteins; 0/Trans-Activators |
| Comments/Corrections | |
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