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Hepatitis C virus core protein enhances Telomerase activity in Huh7 cells.
- Source :
-
Journal of medical virology [J Med Virol] 2010 Feb; Vol. 82 (2), pp. 239-48. - Publication Year :
- 2010
-
Abstract
- Hepatitis C is an oncogenic virus although the mechanisms responsible for this behavior are not clear. We studied the effects of hepatitis C virus (HCV) core protein expression on Telomerase, an enzyme closely associated with cellular immortalization and neoplasia. The aim of this study was to investigate the effects of HCV core protein on the regulation of Telomerase activity in human hepatoma cells. Regulation and expression of human Telomerase reverse transcriptase (TERT) was compared in Huh7 cells stably transfected with HCV core protein or cells expressing vector alone. Telomerase activity was measured using Quantitative Telomerase Detection (QTD) and telomere length was measured by fluorescence in situ hybridization (FISH). Transient transfection and luciferase assay were used to evaluate TERT promoter activity. Telomerase activity was increased twofold in Huh7 cells expressing HCV core protein compared to controls (P < 0.01). This was accompanied by a 1.4-fold increase of TERT mRNA and 1.9-fold increase in TERT protein (P < 0.01 in either case). Cellular fractionation and immunocytochemical studies showed increased localization of TERT in the nucleus of core-expressing cells as compared to controls. FISH assay confirmed that telomeres of HCV core-expressing Huh7 cells were relatively longer than those of control cells (0.22 + 0.05 vs. 0.12 + 0.03, P < 0.01). TERT promoter activity was enhanced about 30% in HCV core-expressing Huh7 cells compared to control cells (P < 0.02). HCV core protein is associated with increased Telomerase activity in hepatoma cells. These findings suggest that enhancement of Telomerase activity by HCV core protein may contribute to the oncogenicity of HCV.<br /> ((c) 2009 Wiley-Liss, Inc.)
- Subjects :
- Artificial Gene Fusion
Cell Line, Tumor
Cell Nucleus chemistry
Gene Expression Profiling
Genes, Reporter
Humans
In Situ Hybridization, Fluorescence methods
Luciferases biosynthesis
Luciferases genetics
Telomere genetics
Up-Regulation
Hepacivirus pathogenicity
Hepatocytes virology
Host-Pathogen Interactions
Telomerase biosynthesis
Viral Core Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1096-9071
- Volume :
- 82
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of medical virology
- Publication Type :
- Academic Journal
- Accession number :
- 20029802
- Full Text :
- https://doi.org/10.1002/jmv.21644