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Hepatitis C Virus Core Protein (hepatitis + c_virus_core_protein)

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Medical Sciences100%

Selected Abstracts

Hepatitis C virus core protein activates ERK and p38 MAPK in cooperation with ethanol in transgenic mice

HEPATOLOGY, Issue 4 2003
Takeya Tsutsumi
In human chronic hepatitis C, alcohol intake is a synergistic factor for the acceleration of hepatocarcinogenesis. Recently, we showed a significant increase of reactive oxygen species (ROS) in hepatitis C virus (HCV) core-transgenic mice fed ethanol-containing diets. Because previous studies indicated that ROS is closely associated with mitogen-activated protein kinases (MAPK), we examined activities of c-Jun N-terminal kinase, p38 MAPK, and extracellular signal-regulated kinase (ERK) in the liver of core-transgenic and nontransgenic mice with short-term ethanol feeding. Activity of ERK and p38 MAPK was increased in core-transgenic mice compared with nontransgenic mice, whereas neither ERK nor p38 MAPK was activated in core-transgenic mice with normal diets. In addition, activity of cyclic-AMP and serum responsive element, downstream pathways of p38 MAPK and ERK, was also increased. Comparison of gene expression profiles by cDNA microarray and real-time PCR revealed that galectin-1, which is associated with cell transformation, was significantly increased in ethanol-fed core-transgenic mice. On the other hand, glutathione S-transferase (GST), which plays a key role in protecting cells from oxidative stress, was decreased. In conclusion, these results suggest that HCV core protein cooperates with ethanol for the activation of some MAPK pathways, and leads to the modulation of several genes, contributing to the pathogenesis of liver disease of HCV- infected patients with high ethanol consumption. (Hepatology 2003;38:820,828). [source]

Hepatitis C virus core protein induces malignant transformation of biliary epithelial cells by activating nuclear factor-,B pathway

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 7 2010
Zhi-Hua Li
Abstract Background and Aim:, In an earlier study, we found that hepatitis C virus core protein, HCV-C, participated in the malignant transformation of HCV-C transfected normal human biliary epithelial (hBE) cells by activating telomerase. Here we further investigated the signaling of the malignant transformation. Methods:, Reverse transcription-polymerase chain reaction (RT-PCR), western blotting and immunoprecipitation were used to analyze the expression of HCV-C, human telomerase reverse transcriptase (hTERT), nuclear factor-,B (NF-,B) and NF-,B inhibitor alpha (I,B,) genes and the phosphorylation level of I,B, protein. Electrophoretic mobility shift assays (EMSA) and NF-,B-linked luciferase reporter assays were carried out to measure NF-,B activity. Results:, The expression of HCV-C and hTERT was detected only in HCV-C-transfected hBE (hBE-HCV-C) cells but not in vector-transfected or parental hBE cells. More NF-,B protein accumulated in nuclear extracts of hBE-HCV-C cells rather than in those of control cells, though total NF-,B protein level showed no difference among these cells. DNA binding activity of NF-,B and the NF-,B-linked luciferase activity were much higher in HCV-C-transfected hBE cells than those in vector- or non-transfected hBE cells. In addition, the I,B, phosphorylation level, but not the I,B, mRNA or protein levels, was increased after HCV-C transfection. Conclusions:, Hepatitis C virus core protein activates NF-,B pathway in hBE cells by increasing the phosphorylation of I,B,. The pathway may be responsible for HCV-C-induced malignant transformation of hBE cells. [source]

Dual effects of hepatitis C virus Core protein on the transcription of cyclin-dependent kinase inhibitor p21 gene

JOURNAL OF VIRAL HEPATITIS, Issue 4 2003
H. J. Kwun
Summary. Transcription of p21 was activated in hepatitis C virus (HCV) Core-expressing HepG2 cells where its upstream p53 was stabilized. However, this effect was not absolutely required for the activation of p21 by Core, as demonstrated in Hep3B cells. In addition, an opposite effect on the transcription of p21 was observed in NIH3T3 and primary hepatocytes, where p53 was not decreased by Core. To explain the p53-independent regulation of p21 by Core, we identified a Core-responsive element between positions ,74 and ,83 of the p21 promoter, exactly overlapped with a tumour growth factor , (TGF- ,)/butyrate responsive element. Furthermore, we demonstrated that Core could activate the p21 through the element by stimulating a butyrate pathway, whereas this was inhibited through a TGF- , pathway. The opposing effects of Core protein on the transcription of p21 might be important in understanding the progression of hepatic disease in HCV-positive patients. [source]

Differential regulation of SOCS-1 signalling in B and T lymphocytes by hepatitis C virus core protein

IMMUNOLOGY, Issue 2 2008
Zhi Qiang Yao
Summary Hepatitis C virus (HCV) infection is characterized by a strong propensity toward chronicity, autoimmune phenomena and lymphomagenesis, supporting a role for lymphocyte dysregulation during persistent viral infection. We have shown that HCV core protein inhibits T-cell functions through interaction with a complement receptor, gC1qR. Here, we further report that B cells also express gC1qR that can be bound by HCV core protein. Importantly, using flow cytometry, we demonstrated differential regulation of B and T lymphocytes by the HCV core,gC1qR interaction, with down-regulation of CD69 activation in T cells but up-regulation of CD69 activation and cell proliferation in B cells. HCV core treatment led to decreased interferon-, production in CD8+ T cells but to increased immunoglobulin M and immunoglobulin G production as well as cell surface expression of costimulatory and chemokine receptors, including CD86 (B7-2), CD154 (CD40L) and CD195 (CCR5), in CD20+ B cells. Finally, we showed down-regulation of suppressor of cytokine signalling-1 (SOCS-1) using real-time reverse transcription,polymerase chain reaction, accompanied by up-regulation of signal transducer and activator of transcription-1 (STAT1) phosphorylation in B cells in response to HCV core protein, with the opposite pattern observed in HCV core-treated T cells. This study demonstrates differential regulation of B and T lymphocytes by HCV core and supports a mechanism by which lymphocyte dysregulation occurs in the course of persistent HCV infection. [source]

Hepatitis C virus core protein induces malignant transformation of biliary epithelial cells by activating nuclear factor-,B pathway

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 7 2010
Zhi-Hua Li
Abstract Background and Aim:, In an earlier study, we found that hepatitis C virus core protein, HCV-C, participated in the malignant transformation of HCV-C transfected normal human biliary epithelial (hBE) cells by activating telomerase. Here we further investigated the signaling of the malignant transformation. Methods:, Reverse transcription-polymerase chain reaction (RT-PCR), western blotting and immunoprecipitation were used to analyze the expression of HCV-C, human telomerase reverse transcriptase (hTERT), nuclear factor-,B (NF-,B) and NF-,B inhibitor alpha (I,B,) genes and the phosphorylation level of I,B, protein. Electrophoretic mobility shift assays (EMSA) and NF-,B-linked luciferase reporter assays were carried out to measure NF-,B activity. Results:, The expression of HCV-C and hTERT was detected only in HCV-C-transfected hBE (hBE-HCV-C) cells but not in vector-transfected or parental hBE cells. More NF-,B protein accumulated in nuclear extracts of hBE-HCV-C cells rather than in those of control cells, though total NF-,B protein level showed no difference among these cells. DNA binding activity of NF-,B and the NF-,B-linked luciferase activity were much higher in HCV-C-transfected hBE cells than those in vector- or non-transfected hBE cells. In addition, the I,B, phosphorylation level, but not the I,B, mRNA or protein levels, was increased after HCV-C transfection. Conclusions:, Hepatitis C virus core protein activates NF-,B pathway in hBE cells by increasing the phosphorylation of I,B,. The pathway may be responsible for HCV-C-induced malignant transformation of hBE cells. [source]

Properties of the hepatitis C virus core protein: a structural protein that modulates cellular processes

JOURNAL OF VIRAL HEPATITIS, Issue 1 2000
McLauchlan
The core protein of hepatitis C virus (HCV) is believed to form the capsid shell of virus particles. Maturation of the protein is achieved through cleavage by host cell proteases to give a product of 21 000 MW, which is found in tissue culture systems and sera from infected individuals. However, efficient propagation of the virus is not possible at present in tissue culture. Hence, studies have focused on the properties of the core protein and its possible role in pathologies associated with HCV infection. This review describes key features of the polypeptide and the status of current knowledge on its ability to influence several cellular processes. [source]