Document Detail

Dysregulation of hepatocyte cell cycle and cell viability by hepatitis B virus.
MedLine Citation:
PMID:  19786052     Owner:  NLM     Status:  MEDLINE    
BACKGROUND/AIMS: Dysregulation of the cell cycle is frequently associated with tumor development. Hepatitis B virus (HBV) is associated with a significant risk of developing hepatocellular carcinoma but the effects of HBV on cell cycle regulation are not completely understood. METHODS: We have used a recombinant adeno-HBV model system to investigate the effect of infection with HBV and the replication defective lamivudine resistant mutant rtM204I mutant on hepatocyte cell cycle and cell viability. RESULTS: Huh7 cells synchronised at the G1/S phase of the cell cycle were arrested at the G2/M following infection with rAdHBV-wt and rAdHBV-M204I. This was accompanied by increased levels of p21(cip1), p-cdc2, cyclins D, A and B. Cell viability was reduced and cleaved caspase 3 levels were increased in HBV- and rtM204I-infected cells. rAdHBV-M204I-infected Huh7 cells also demonstrated significant up-regulation of phospho-ERK, phospho-Akt, p53 and phospho-Mdm2 compared to mock-infected cells. These changes were comparable to those following infection of Huh7 cells with rAdHBV-wt. CONCLUSION: Our results suggest that HBV, regardless of phenotype, produces cell cycle arrest and reduced hepatocyte viability. Perturbations in these cellular processes are likely to underlie HBV-associated liver oncogenic transformation and may help explain the ongoing risk of developing hepatocellular carcinoma in individuals in whom the lamivudine resistant rtM204I mutant emerges.
Ruth Chin; Ulrich Nachbur; Linda Earnest-Silveira; Aleksandra Bankovacki; Bernd Koeberlein; Hanswalter Zentgraf; C-Thomas Bock; John Silke; Joseph Torresi
Publication Detail:
Type:  Journal Article     Date:  2009-09-26
Journal Detail:
Title:  Virus research     Volume:  147     ISSN:  1872-7492     ISO Abbreviation:  Virus Res.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2009-12-09     Completed Date:  2010-02-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8410979     Medline TA:  Virus Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  7-16     Citation Subset:  IM    
Department of Medicine, Austin Hospital, University of Melbourne, Heidelberg, Victoria 3084, Australia.
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MeSH Terms
Cell Cycle*
Cell Cycle Proteins / analysis
Cell Line
Cell Survival
Hepatitis B virus / pathogenicity*
Hepatocytes / chemistry,  physiology*,  virology*
Protein Kinases / analysis
Signal Transduction
Reg. No./Substance:
0/Cell Cycle Proteins; EC 2.7.-/Protein Kinases

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

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