PMID- 20029802
OWN - NLM
STAT- MEDLINE
DCOM- 20100303
LR  - 20211020
IS  - 1096-9071 (Electronic)
IS  - 0146-6615 (Linking)
VI  - 82
IP  - 2
DP  - 2010 Feb
TI  - Hepatitis C virus core protein enhances Telomerase activity in Huh7 cells.
PG  - 239-48
LID - 10.1002/jmv.21644 [doi]
AB  - 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.
CI  - (c) 2009 Wiley-Liss, Inc.
FAU - Zhu, Zhaowen
AU  - Zhu Z
AD  - Department of Internal Medicine and Research Service, Veterans Administration 
      Medical Center, Iowa City, Iowa, USA.
FAU - Wilson, Anne T
AU  - Wilson AT
FAU - Gopalakrishna, Kota
AU  - Gopalakrishna K
FAU - Brown, Kyle E
AU  - Brown KE
FAU - Luxon, Bruce A
AU  - Luxon BA
FAU - Schmidt, Warren N
AU  - Schmidt WN
LA  - eng
GR  - I01 BX000159/BX/BLRD VA/United States
GR  - R21 DK068453/DK/NIDDK NIH HHS/United States
GR  - R21 DK068453-01A1/DK/NIDDK NIH HHS/United States
GR  - R01 DK058597-4/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - J Med Virol
JT  - Journal of medical virology
JID - 7705876
RN  - 0 (Viral Core Proteins)
RN  - 0 (nucleocapsid protein, Hepatitis C virus)
RN  - EC 1.13.12.- (Luciferases)
RN  - EC 2.7.7.49 (Telomerase)
SB  - IM
MH  - Artificial Gene Fusion
MH  - Cell Line, Tumor
MH  - Cell Nucleus/chemistry
MH  - Gene Expression Profiling
MH  - Genes, Reporter
MH  - Hepacivirus/*pathogenicity
MH  - Hepatocytes/*virology
MH  - *Host-Pathogen Interactions
MH  - Humans
MH  - In Situ Hybridization, Fluorescence/methods
MH  - Luciferases/biosynthesis/genetics
MH  - Telomerase/*biosynthesis
MH  - Telomere/genetics
MH  - Up-Regulation
MH  - Viral Core Proteins/*metabolism
EDAT- 2009/12/24 06:00
MHDA- 2010/03/04 06:00
CRDT- 2009/12/24 06:00
PHST- 2009/12/24 06:00 [entrez]
PHST- 2009/12/24 06:00 [pubmed]
PHST- 2010/03/04 06:00 [medline]
AID - 10.1002/jmv.21644 [doi]
PST - ppublish
SO  - J Med Virol. 2010 Feb;82(2):239-48. doi: 10.1002/jmv.21644.