Document Detail


Human herpesvirus 6B inhibits cell proliferation by a p53-independent pathway.
MedLine Citation:
PMID:  17276372     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Various forms of cellular stress can activate the tumour suppressor protein p53, an important regulator of cell cycle arrest, apoptosis, and cellular senescence. Cells infected by human herpesvirus 6B (HHV-6B) accumulate aberrant amounts of p53. OBJECTIVES: The aim of this study was to investigate the role of p53 accumulation in the HHV-6B-induced cell cycle arrest. STUDY DESIGN: The role of p53 was studied using the p53 inhibitor pifithrin-a, and cells genetically deficient in functional p53 by homologous recombination. RESULTS: In response to HHV-6B infection, epithelial cells were arrested in the G1/S phase of the cell cycle concomitant with an aberrant accumulation of p53. However, the known p53-induced mediator of cell cycle arrest, p21, was not upregulated. Approximately 90% of the cells expressed HHV-6B p41, indicative of viral infection. The presence of pifithrin-a, a p53 inhibitor, did not reverse the HHV-6B-induced cell cycle block. In support of this, HHV-6B infection of p53(-/-) cells induced a cell cycle block before S-phase with kinetics similar to or faster than that observed by infection in wt cells. CONCLUSIONS: HHV-6B infection inhibited host cell proliferation concomitantly with p53 accumulation, but importantly the block in cell cycle occurred by a pathway independent of p53.
Authors:
Bodil Øster; Maja D Kaspersen; Emil Kofod-Olsen; Bettina Bundgaard; Per Höllsberg
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology     Volume:  37 Suppl 1     ISSN:  1386-6532     ISO Abbreviation:  J. Clin. Virol.     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2007-02-05     Completed Date:  2007-08-21     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9815671     Medline TA:  J Clin Virol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  S63-8     Citation Subset:  IM    
Affiliation:
Institute of Medical Microbiology and Immunology, University of Aarhus, Aarhus, Denmark.
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MeSH Terms
Descriptor/Qualifier:
Benzothiazoles / pharmacology
Cell Cycle
Cell Line
Cell Proliferation*
Cyclin-Dependent Kinase Inhibitor p21 / biosynthesis
DNA-Binding Proteins / biosynthesis
Herpesvirus 6, Human / physiology*
Humans
Toluene / analogs & derivatives,  pharmacology
Tumor Suppressor Protein p53 / antagonists & inhibitors,  biosynthesis,  physiology*
Viral Proteins / biosynthesis
Virus Replication
Chemical
Reg. No./Substance:
0/Benzothiazoles; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/DNA-Binding Proteins; 0/Tumor Suppressor Protein p53; 0/Viral Proteins; 0/pifithrin; 108-88-3/Toluene; 138415-18-6/p41 protein, Human herpesvirus 6

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