scholarly journals Serodiagnosis of hepatitis C virus (HCV) infection with an HCV core protein molecularly expressed by a recombinant baculovirus.

1991 ◽  
Vol 88 (11) ◽  
pp. 4641-4645 ◽  
Author(s):  
J. Chiba ◽  
H. Ohba ◽  
Y. Matsuura ◽  
Y. Watanabe ◽  
T. Katayama ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Core Protein ◽  
Recombinant Baculovirus ◽  
Hcv Infection ◽  
Hcv Core Protein

scholarly journals Proteasome Activator PA28γ-Dependent Nuclear Retention and Degradation of Hepatitis C Virus Core Protein

2003 ◽  
Vol 77 (19) ◽  
pp. 10237-10249 ◽  
Author(s):  
Kohji Moriishi ◽  
Tamaki Okabayashi ◽  
Kousuke Nakai ◽  
Kyoji Moriya ◽  
Kazuhiko Koike ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Core Protein ◽  
Regulatory Protein ◽  
Hcv Infection ◽  
Nuclear Retention ◽  
Proteasome Activator ◽  
Hcv Core Protein ◽  
Core Proteins ◽  
Chronic Hcv

ABSTRACT Hepatitis C virus (HCV) core protein plays an important role in the formation of the viral nucleocapsid and a regulatory protein involved in hepatocarcinogenesis. In this study, we have identified proteasome activator PA28γ (11S regulator γ) as an HCV core binding protein by using yeast two-hybrid system. This interaction was demonstrated not only in cell culture but also in the livers of HCV core transgenic mice. These findings are extended to human HCV infection by the observation of this interaction in liver specimens from a patient with chronic HCV infection. Neither the interaction of HCV core protein with other PA28 subtypes nor that of PA28γ with other Flavivirus core proteins was detected. Deletion of the PA28γ-binding region from the HCV core protein or knockout of the PA28γ gene led to the export of the HCV core protein from the nucleus to the cytoplasm. Overexpression of PA28γ enhanced the proteolysis of the HCV core protein. Thus, the nuclear retention and stability of the HCV core protein is regulated via a PA28γ-dependent pathway through which HCV pathogenesis may be exerted.

Hepatitis C Virus (HCV) Infection, Monoclonal Immunoglobulin Specific for HCV Core Protein, and Plasma-Cell Malignancy

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2712-2712
Author(s):  
Edith Bigot-Corbel ◽  
Michelle Gassin ◽  
Isabelle Corre ◽  
Didier Le Carrer ◽  
Odile Delaroche ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Plasma Cell ◽  
Core Protein ◽  
Hcv Infection ◽  
Monoclonal Immunoglobulin ◽  
Hcv Core Protein ◽  
Increased Risk ◽  
Genotype 2 ◽  
Cell Malignancy

Abstract Hepatitis C virus (HCV) infection can lead to B-cell malignancy via direct infection and transformation of B-lymphocytes, or via indirect transformation by chronic antigen-driven stimulation. Both mechanisms may occur simultaneously, as we previously reported in a case of HCV infection followed by plasma-cell leukemia (PCL), where blasts were infected with HCV and the monoclonal immunoglobulin (Ig) they produced was directed against the core protein of the virus (New Engl J Med, 2003; 348:178). Approximately 10% of HCV-positive patients develop a monoclonal Ig, the specificity of which is usually unknown. To evaluate the link between chronic HCV-antigen driven stimulation and plasma–cell transformation, we studied the specificity of monoclonal Ig developed in the context of HCV infection. Over a period of 13 months, sera from patients consulting or hospitalised at the Centre Hospitalier Universitaire of Nantes found positive for monoclonal Ig, were systematically tested for the presence of HCV RNA and anti-HCV Ig. Among the 700 patients thus studied, 10 (1.4%) were found positive for HCV. Purification of the monoclonal Ig was achieved for 7/10 patients. Using immunoblotting, the purified monoclonal Ig (2 IgG, 1 IgA, 1 IgM) of 4 patients, all with HCV genotype 2, recognized the C22–3 fragment of HCV-core protein; 2 (IgG) recognized NS-4 and 1 did not recognize HCV. Among the 4 patients with anti-HCV-core monoclonal Ig, two presented with mixed (type II) cryoglobulinemia and one was diagnosed with multiple myeloma. Hence, 2/5 patients with anti-HCV core monoclonal Ig developed plasma-cell malignancy. Anti-HCV treatment resulted in the disappearance of the monoclonal Ig for 3/3 treated patients. In summary, in the context of HCV infection monoclonal Ig were typically directed against the virus, and could distinguish patients with increased risk of plasma-cell malignancy. Efforts should be made to identify such patients, as anti-viral therapy should help eradicate the HCV-driven plasma-cell clone.

Hepatitis C virus (HCV) infection, monoclonal immunoglobulin specific for HCV core protein, and plasma-cell malignancy

Blood ◽  
2008 ◽  
Vol 112 (10) ◽  
pp. 4357-4358 ◽  
Author(s):  
Edith Bigot-Corbel ◽  
Michelle Gassin ◽  
Isabelle Corre ◽  
Didier Le Carrer ◽  
Odile Delaroche ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Plasma Cell ◽  
Core Protein ◽  
Hcv Infection ◽  
Monoclonal Immunoglobulin ◽  
Hcv Core Protein ◽  
Cell Malignancy

scholarly journals Hepatitis C Virus Core Protein Augments Androgen Receptor-Mediated Signaling

2008 ◽  
Vol 82 (22) ◽  
pp. 11066-11072 ◽  
Author(s):  
Tatsuo Kanda ◽  
Robert Steele ◽  
Ranjit Ray ◽  
Ratna B. Ray
Keyword(s):  
Hepatitis C Virus ◽  
Androgen Receptor ◽  
Hepatitis C ◽  
Signaling Pathway ◽  
Core Protein ◽  
Tube Formation ◽  
Hcv Infection ◽  
Vegf Expression ◽  
Virus Core ◽  
Hcv Core Protein

ABSTRACT Hepatitis C virus (HCV) infection is frequently associated with the development of hepatocellular carcinoma (HCC), which is one of the male-dominant diseases. Androgen signaling in liver may be related to carcinogenesis. In this study, we investigated whether HCV proteins cross talk with the androgen receptor (AR) signaling pathway for promotion of carcinogenesis. We have demonstrated that HCV core protein alone or in context with other HCV proteins enhances AR-mediated transcriptional activity and further augments in the presence of androgen. Subsequent study suggested that HCV core protein activates STAT3, which in turn enhances AR-mediated transcription. This activity was blocked by a pharmacological inhibitor of the Jak/Stat signaling pathway, AG490. Vascular endothelial growth factor (VEGF) is a target gene of AR in liver and plays an important role in angiogenesis. Therefore, we examined whether HCV infection modulates VEGF expression in hepatocytes. Our results demonstrated that HCV enhances VEGF expression and facilitates tube formation in human coronary microvascular endothelial cells in the presence of AR. Together, our results suggest that HCV core protein acts as a positive regulator in AR signaling, providing further insight into oncogenic potential in the development of HCC in HCV-infected individuals.

scholarly journals Differential Effects on the Hepatitis C Virus (HCV) Internal Ribosome Entry Site by Vitamin B12 and the HCV Core Protein

2004 ◽  
Vol 78 (21) ◽  
pp. 12075-12081 ◽  
Author(s):  
Dongsheng Li ◽  
William B. Lott ◽  
John Martyn ◽  
Gholamreza Haqshenas ◽  
Eric J. Gowans
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Internal Ribosome Entry Site ◽  
Core Protein ◽  
Vitamin B ◽  
Entry Site ◽  
Internal Ribosome Entry ◽  
Hcv Core Protein ◽  
Hcv Ires

ABSTRACT To investigate the role of the hepatitis C virus internal ribosome entry site (HCV IRES) domain IV in translation initiation and regulation, two chimeric IRES elements were constructed to contain the reciprocal domain IV in the otherwise HCV and classical swine fever virus IRES elements. This permitted an examination of the role of domain IV in the control of HCV translation. A specific inhibitor of the HCV IRES, vitamin B12, was shown to inhibit translation directed by all IRES elements which contained domain IV from the HCV and the GB virus B IRES elements, whereas the HCV core protein could only suppress translation from the wild-type HCV IRES. Thus, the mechanisms of translation inhibition by vitamin B12 and the core protein differ, and they target different regions of the IRES.

Hepatitis C virus (HCV) core protein enhances the immunogenicity of a co-delivered DNA vaccine encoding HCV structural antigens in mice

2006 ◽  
Vol 44 (1) ◽  
pp. 9 ◽  
Author(s):  
Marleny González ◽  
Liz Alvarez-Lajonchere ◽  
Julio César Alvarez-Obregón ◽  
Ivis Guerra ◽  
Ariel Viña ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Dna Vaccine ◽  
Core Protein ◽  
Hcv Core Protein

Hepatitis C virus core protein inhibits hepatitis B virus replication by downregulating HBx levels via Siah-1-mediated proteasomal degradation during coinfection

2021 ◽  
Vol 102 (12) ◽  
Author(s):  
Sujeong Lee ◽  
Hyunyoung Yoon ◽  
Jiwoo Han ◽  
Kyung Lib Jang
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Core Protein ◽  
Experimental Studies ◽  
Proteasomal Degradation ◽  
Hbv Replication ◽  
Hcv Core Protein ◽  
B Virus

Most clinical and experimental studies have suggested that hepatitis C virus (HCV) is dominant over hepatitis B virus (HBV) during coinfection, although the mechanism remains unclear. Here, we found that HCV core protein inhibits HBV replication by downregulating HBx levels during coinfection in human hepatoma cells. For this effect, HCV core protein increased reactive oxygen species levels in the mitochondria and activated the ataxia telangiectasia mutated-checkpoint kinase two pathway in the nucleus, resulting in an upregulation of p53 levels. Accordingly, HCV core protein induced p53-dependent activation of seven in absentia homolog one expression, an E3 ligase of HBx, resulting in the ubiquitination and proteasomal degradation of HBx. The effect of the HCV core protein on HBx levels was accurately reproduced in both a 1.2-mer HBV replicon and in vitro HBV infection systems, providing evidence for the inhibition of HBV replication by HCV core protein. The present study may provide insights into the mechanism of HCV dominance in HBV- and HCV-coinfected patients.

scholarly journals Induction of HOX genes by HCV infection via impairment of histone H2A monoubiquitination.

2020 ◽  
pp. JVI.01784-20
Author(s):  
Hirotake Kasai ◽  
Kazuki Mochizuki ◽  
Tomohisa Tanaka ◽  
Atsuya Yamashita ◽  
Yoshiharu Matsuura ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Protein Expression ◽  
Hox Genes ◽  
Core Protein ◽  
Gene Promoter ◽  
Hcv Infection ◽  
Histone H2a ◽  
Hox Gene ◽  
The Core ◽  
Hcv Core Protein

Hepatitis C virus (HCV) infection causes liver pathologies, including hepatocellular carcinoma (HCC). Homeobox (HOX) gene products regulate embryonic development and are associated with tumorigenesis, although the regulation of HOX genes by HCV infection has not been clarified in detail. We examined the effect of HCV infection on HOX gene expression. In this study, HCV infection induced more than half of the HOX genes and reduced the level of histone H2A monoubiquitination on lysine (K) 119 (H2Aub), which represses HOX gene promoter activity. HCV infection also promoted proteasome-dependent degradation of RNF2, which is an E3 ligase mediating H2A monoubiquitination as a component of polycomb repressive complex 1. Since full-genomic replicon cells but not subgenomic replicon cells exhibited reduced RNF2 and H2Aub levels and induction of HOX genes, we focused on the core protein. Expression of the core protein reduced the amounts of RNF2 and H2Aub and induced HOX genes. Treatment with LY-411575, which can reduce HCV core protein expression via SPP inhibition without affecting other viral proteins, dose-dependently restored the amounts of RNF2 and H2Aub in HCV-infected cells and impaired the induction of HOX genes and production of viral particles but not viral replication. The chromatin immunoprecipitation assay results also indicated infection- and proteasome-dependent reductions in H2Aub located in HOX gene promoters. These results suggest that HCV infection or core protein induces HOX genes by impairing histone H2A monoubiquitination via a reduction in the RNF2 level.Importance Recently sustained virologic response can be achieved by direct acting antiviral therapy in most of hepatitis C patients. Unfortunately, DAA therapy does not completely eliminate a risk of HCC. Several epigenetic factors, including histone modifications, are well known to contribute to HCV-associated HCC. However, the regulation of histone modifications by HCV infection has not been clarified in detail. In this study, our data suggest that HCV infection or HCV core protein expression impairs monoubiquitination of histone H2A K119 in HOX gene promoter via destabilization of RNF2 and then induces HOX genes. Several lines of evidence suggest that the expression of several HOX genes is dysregulated in certain types of tumors. These findings reveal a novel mechanism of HCV-related histone modification and may provide information about new targets for diagnosis and prevention of HCC occurrence.

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