• IMMUNE NETWORK
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• v.6 no.1
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• pp.20-26
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• 2006

Background: Rheumatoid arthritis (RA) is a chronic and systemic inflammatory disease that is characterized by invasive synovial hyperplasia, leading to progressive joint destruction. Recent studies have described that RA is caused by virus, bacteria or outside material. Approximately 2 to 20% of RA cases arc reported to be associated with infected hepatitis C virus (HCV). However, the mechanisms underlying virus-induced RA are still unknown. Moreover, few molecular studies have addressed the inflammatory aspects of HCV-associated autoimmune RA. In this study, we aimed to determine whe ther or not another HCV core protein transactivates the IL-8 gene expression, prototypic chemokine, in synovial cell. Methods: To establish the HCV core expressing stable synovial cell line, pCI-neo-core, a plasmid encoding HCV core protein, were transfected to HIG-82 cell line that is an established cell line from rabbit periaricular soft tissue. We examined the morphological changes and cell cycle distribution of HIG-82 cells with expression of HCV core protein by inverted microscopy and flow cytometry analysis, respectively. Also, we determined the mRNA levels of Interleukin (IL)-6 and IL-8 related to the inflammation by RT-PCR and then analyzed regulation of IL-8 expression by the NF-${\kappa}B$ pathway. Results: Our study showed no significant differences in morphology and cell cycle between HIG-82 control cell line and HIG-82 expressing HCV core protein. However, expression of HCV core protein induces the IL-8 mRNA expression in HIG-82 core cells via activated NF-${\kappa}B$ pathway. Conclusion: These results suggest that HCV core protein can lead to enhanced IL-8 expression. Such a proinflammatory role may contribute to the etiologic pathogenesis in RA patients with HCV infection.

• Bulletin of the Korean Chemical Society
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• v.27 no.11
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• pp.1919-1922
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• 2006

• BMB Reports
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• v.33 no.1
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• pp.59-62
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• 2000

Hepatitis C virus (HCV) nonstructural 5B (NS5B) protein is an RNA-dependent RNA polymerase (RdRp). To determine whether it can contribute to viral replication by interaction with cellular proteins, the yeast two-hybrid screening system was employed to screen a human liver cDNA library. Using the HCV NS5B as a bait, we have isolated positive clones encoding a cellular protein. The NS5B interacting protein, 5BIP, is a novel cellular protein of 170 amino acids. Interaction of the HCV NS5B protein with 5BIP was confirmed by a protein-protein blotting assay. Recently, we have demonstrated that NS5B possesses an RdRp activity and thus it is possible that 5BIP, in association with NS5B, plays a role in HCV replication.

• Biomolecules & Therapeutics
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• v.17 no.2
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• pp.151-155
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• 2009

Hepatitis C virus (HCV) has genetic diversity like most of RNA viruses. HCV major genotypes are classified into several subtypes which are further divided into quasispecies having, genetically different but closely related variants. The HCV core that is a nucleocapsid protein located at the amino terminus of the viral polyprotein is relatively a conserved protein among the HCV isolates and thus it has been one of plausible targets for anti-HCV drug development. However, different quasispecies of HCV core gene have also been found. In this study, we compared the expression level of core protein between two different quasispecies of HCV genotype 1b. Our data demonstrate that a little differences of amino acid sequence lead to substantial difference of expression level. It might be another important reason of different pathogenesis among HCV infected patients.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.1
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• pp.235-238
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• 2016

Hepatitis C is an ailment of liver caused by hepatitis C virus (HCV) infection. About 3% of the world population is infected by this virus. HCV infection is a leading reason for liver cirrhosis and therefore a major source of hepatocellular carcinoma. The study focused on the incidence of active HCV infection in blood donors of Mardan district of KPK, Pakistan. A total of 5318 blood donors were inspected for the presence of anti-HCV antibodies and HCV-RNA using ICT (immune-chromatographic test), ELISA and RT-PCR at Mardan Medical Complex (MMC), Mardan. Out of these, 157 (2.95%) were positive by ICT, 60 (1.12%) by ELISA and 56 (1.05%) for HCV-RNA. The frequency of active HCV infectivity amongst the blood donors from district Mardan, KPK Pakistan was 1.05 %. Application of strict measures during blood donor selection and use of proper screening assays such as ELISA in place of ICT devices can give a more accurate picture so that the incidence of this viral infection in HCV negative blood recipients can be reduced.

• Microbiology and Biotechnology Letters
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• v.36 no.4
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• pp.353-359
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• 2008

Hepatitis C virus (HCV) is known as the causative agent of blood transmitted hepatitis. Two viral proteins, E2 and NS5A, are known to exert interferon resistance of HCV via PKR pathway. Here, we report a third protein, the RNA-dependent RNA polymerase (NS5B) of HCV, induced interferon resistance inhibiting p56 pathway. p56 was shown to interact with p48 subunit of eukaryotic initiation factor 3 (eIF3). This interaction inhibited formation of ternary complex in translation initiation. Using dual reporter assay system, we observed that the translation decreased when interferon alpha was added to the culture. But, in the presence of HCV NS5B, the translation partly recovered. NS5B and p48 subunit of eIF3 were shown to interact. This interaction seems to inhibit the interaction between p48 and p56. This is the first report that a virus exerts interferon resistance via p56 pathway.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.5
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• pp.375-383
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• 2013

Hepatocellular carcinoma (HCC) related to hepatitis B virus (HBV) and hepatitis C virus (HCV) infections is thought to account for more than 80% of primary liver cancers. Both HBV and HCV can establish chronic liver inflammatory infections, altering hepatocyte and liver physiology with potential liver disease progression and HCC development. Cyclophilin A (CypA) has been identified as an essential host factor for the HCV replication by physically interacting with the HCV non structural protein NS5A that in turn interacts with RNA-dependent RNA polymerase NS5B. CypA, a cytosolic binding protein of the immunosuppressive drug cyclosporine A, is overexpressed in many cancer types and often associated with malignant transformation. Therefore, CypA can be a good target for molecular cancer therapy. Because of antiviral activity, the CypA inhibitors have been tested for the treatment of chronic hepatitis C. Nonimmunosuppressive Cyp inhibitors such as NIM811, SCY-635, and Alisporivir have attracted more interests for appropriating CypA for antiviral chemotherapeutic target on HCV infection. This review describes CypA inhibitors as a potential HCC treatment tool that is contrived by their obstructing chronic HCV infection and summarizes roles of CypA in cancer development.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.5
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• pp.2699-2703
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• 2016

Background: Primary hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. MicroRNAs (miRNAs) have great HCC diagnostic potential and circulating miRNAs have been reported as promising biomarkers for various pathologic conditions. Aim: To explore the potential benefit of serum miR-126, miR-129, miR-155, miR-203 and miR-223 as non-invasive diagnostic markers of hepatitis C virus (HCV)-related HCC. Materials and Methods: The expression of miRNA was evaluated using real-time quantitative RT-PCR in 78 serum samples (30 $treatment-na{\ddot{i}}ve$ chronic HCV, 25 post-HCV compensated cirrhosis and 23 $treatment-na{\ddot{i}}ve$ HCC cases). Results: Comparing miRNA fold changes in the HCC group vs the non HCC groups, there was significant fold decrease in miR-126 (P= 0.034), miR-129 (P= 0.006), miR-155 (P= 0.011), miR-203 (P<0.001) and miR-223 (P= 0.013). The highest AUC to differentiate HCC patients from non-HCC was 0.76 for miR-203. Conclusions: Among studied miRNAs, serum miR-203 has the highest potential as a non-invasive biomarker of HCC.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.3
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• pp.1411-1414
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• 2014

Background: Hepatitis B and C are the leading causes of liver diseases worldwide. For hematological and solid malignancy patients undergoing chemotherapy, increases in HBV DNA and HCV RNA levels can be detected which may result in reactivation and hepatitis-related morbidity and mortality. The aim of this study was to determine the seroprevalence of Hbs ag and Anti HCV positivity in patients with solid malignancies undergoing chemotherapy and consequences during follow-up. Materials and Methods: The files of 914 patients with solid malignancies whose hepatitis markers were determined serologically at diagnosis were reviewed retrospectively. All underwent adjuvant/palliative chemotherapy. For the cases with HBV and/or HCV positivity, HBV DNA and HCV RNA levels, liver function tests at diagnosis and during follow-up and the treatment modalities that were chosen were determined. Results: Of 914 cases, Hbs Ag, anti Hbs and anti HCV positivity were detected in 40 (4.4%), 336 (36.8%) and 26 (2.8%) of the cases respectively. All of the Hbs ag positive patients received prophylactic lamuvidine before the start of chemotherapy. In the Hbs ag and anti HCV positive cases, liver failure was not detected during chemotherapy and a delay in chemotherapy courses because of hepatitis was not encountered. Conclusions: Just as with hematological malignancies, screening for HBV and HCV should also be considered for patients with solid tumors undergoing chemotherapy. Prophylactic antiviral therapy for HBV reduces both the reactivation rates and HBV related mortality and morbidity. The clinical impact of HCV infection on patients undergoing chemotherapy is still not well characterized.

• Journal of Yeungnam Medical Science
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• v.9 no.2
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• pp.407-415
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• 1992

Among 85 patients with anti-HCV positive chronic liver disease, only 21.2% have past history of blood transfusion and over half the cases, they do not have any suspicious risk factors for HCV infection, 3 of 85 families show anti-HCV positive family members. On the other hand, 40 of 60 patients with HBsAg positive chronic liver disease show HBsAg positive family members. In Korea, HBV is transmitted mainly through vertical and intrafamilial infection but HCV disease might be rather horizontal and sporadic than vertical. To define the evident source of infection in sporadic hepatitis C, first of all, simple test with high sensitivity and specificity for diagnosis of HCV infection would be needed.