Document Detail


Cell cycle-independent expression of immediate-early gene 3 results in G1 and G2 arrest in murine cytomegalovirus-infected cells.
MedLine Citation:
PMID:  18667506     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Lüder Wiebusch; Anke Neuwirth; Linus Grabenhenrich; Sebastian Voigt; Christian Hagemeier
Related Documents :
16479156 - Tfii-i: connecting mitogenic signals to cell cycle regulation.
16875416 - Perspectives in the coordinate regulation of cell cycle events in synechococcus.
17571276 - The complex p25/cdk5 kinase in neurofibrillary degeneration and neuronal death: the mis...
17141486 - Connecting cell-cycle activation to neurodegeneration in drosophila.
15943606 - Giant cell tumour of bone in a cat with extraskeletal metastases: pathological and immu...
16479156 - Tfii-i: connecting mitogenic signals to cell cycle regulation.
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-07-30
Journal Detail:
Title:  Journal of virology     Volume:  82     ISSN:  1098-5514     ISO Abbreviation:  J. Virol.     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2008-09-30     Completed Date:  2008-10-14     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  10188-98     Citation Subset:  IM    
Affiliation:
Department of Pediatrics, Laboratory for Molecular Biology, Charité-Universitätsmedizin Berlin, Ziegelstr. 5-9, 10117 Berlin, Germany.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
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:
0/IE2 protein, Cytomegalovirus; 0/Immediate-Early Proteins; 0/Trans-Activators
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Murine coronavirus mouse hepatitis virus is recognized by MDA5 and induces type I interferon in brai...
Next Document:  Potent antibody-mediated neutralization and evolution of antigenic escape variants of simian immunod...