• Journal of Microbiology and Biotechnology
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• v.20 no.12
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• pp.1769-1771
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• 2010

The envelope glycoprotein E2 of hepatitis C virus (HCV) binds to various cell surface receptors for viral infection. We performed biopanning against this protein and selected peptides from phage display peptide libraries. Two short peptides, pep7-1 and pep12-1, were selected and their ability to inhibit the infection process was investigated. When pep7-1 was present, the infectivity of HCV particles in cell culture was notably decreased. This decrease was demonstrated by Western blot analysis, immunofluorescence assay, and reverse transcription PCR assay. However, pep12-1 showed little inhibitory effect on HCV infection.

• Bulletin of the Korean Chemical Society
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• v.30 no.11
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• pp.2626-2630
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• 2009

2'($\beta$)-Hydroxymethylated adenosine is a potent and selective inhibitor of hepatitis C virus (HCV) replication. It targets the RNA-dependent RNA polymerase of HCV, NS5B. Synthesis and antiviral evaluation of carbocyclic versions are described. The cyclopentene intermediate ($9\beta$) was successfully synthesized through sequential Johnson-Claisen orthoester rearrangement and ring-closing metathesis (RCM). Coupling of bases via a Pd(0) catalyst, selective dihydroxylation, and desilylation yielded the target nucleoside analogues. The compounds 17 and 18 were assayed for their ability to inhibit HCV RNA replication in a subgenomic replicon Huh7 cell line and showed moderate antiviral activity with toxicity up to 20.0 and 24.7 ${\mu}g/mL$, respectively.

• BMB Reports
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• v.37 no.2
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• pp.192-198
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• 2004

The hepatitis C virus (HCV) core protein is believed to be one of viral proteins that are capable of preventing virus-infected cell death upon various stimuli. But, the effect of the HCV core protein on apoptosis that is induced by various stimuli is contradictory. We examined the possibility that the HCV core protein affects the ceramide-induced cell death in cells expressing the HCV core protein through the sphingomyelin pathway. Cell death that is induced by $C^2$-ceramide and bacterial sphingomyelinase was analyzed in 293 cells that constitutively expressed the HCV core protein and compared with 293 cells that were stably transfected only with the expression vector. The HCV core protein inhibited the cell death that was induced by these reagents. The protective effects of the HCV core protein on ceramide-induced cell death were reflected by the reduced expression of $p21^{WAF1/Cip1/Sid1}$ and the sustained expression of the Bcl-2 protein in the HCV core-expressing cells with respect to the vector-transfected cells. These results suggest that the HCV core protein in 293 cells plays a role in the modulation of the apoptotic response that is induced by ceramide. Also, the ability of the HCV core protein to suppress apoptosis might have important implications in understanding the pathogenesis of the HCV infection.

• Journal of Preventive Medicine and Public Health
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• v.24 no.4 s.36
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• pp.465-472
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• 1991

This study was designed to estimate the prevalence of hepatitis C virus(HCV) infection in drug abusers. The subjects were 141 inpatients who had been admitted to a general hospital with the symptoms and signs of methamphetamine intoxication. Seroprevalence of antibody to the hepatitis C virus(anti-HCV) was 60.3%(85/141) and it was higher in the group with increased frequency and duration of drug abuse, but such a relationship was not found in the seroprevalence of hepatitis B surface antigen(HBsAg). These findings suggested the possibility of high prevalence of HCV infection in methamphetamine abusers, and the importance of repetitive percutaneous injection in the transmission of HCV infection.

• BMB Reports
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• v.38 no.2
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• pp.151-160
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• 2005

By a cDNA array representing 2308 signal transduction related genes, we studied the expression profiles of HeLa cells stably transfected by Hepatitis C virus nonstructural protein 4B (HCV-NS4B). The alterations of the expression of four genes were confirmed by real-time quantitative RT-PCR; and the aldo-keto reductase family 1, member C1 (AKR1C1) enzyme activity was detected in HCV-NS4B transiently transfected HeLa cells and Huh-7, a human hepatoma cell line. Of the 2,308 genes we examined, 34 were up-regulated and 56 were down-regulated. These 90 genes involved oncogenes, tumor suppressors, cell receptors, complements, adhesions, transcription and translation, cytoskeletion and cellular stress. The expression profiling suggested that multiple regulatory pathways were affected by HCV-NS4B directly or indirectly. And since these genes are related to carcinogenesis, host defense system and cell homeostatic mechanism, we can conclude that HCV-NS4B could play some important roles in the pathogenesis mechanism of HCV.

• The Journal of Korean Society of Virology
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• v.27 no.2
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• pp.115-128
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• 1997

Three cDNA fragments located within NS5 region of HCV were synthesized by RT using viral RNA extracted from blood sample of Korean patient as a template. The cDNAs were amplified by PCR, cloned into the T-vector, and the nucleotide sequences were determined. Comparative analysis of the nucleotide and amino acid sequence of NS5 cDNAs showed that it is closely related with HCV type 1b. The cloned NS5 cDNA showed 91-94% homology at the nucleotide sequence level and 96-98% homology at the amino acid sequence level with several strains of the HCV type 1b. The NS5 cDNAs were subcloned into E. coli expression vectors to construct pRSETA5-1, pTHAN5-1, pRSETC5-2, pRSETBB1, pRESTCB1 and pRSETB-H3. Expression of the NS5 proteins was achieved by inducing the promoter with isopropyl-thio-${\beta}$-D-galactoside (IPTG) and confirmed by SDS-polyacrylamide gel electrophoresis. The NS5 proteins were immunoreactive against sera from Korean hepatitis C patients in Western blot analysis. Among the recombinant NS5 proteins, pRSETAS-1 plasmid derived protein, coded from aa2022 to aa2521 of HCV polyprotein, showed the strongest immunoreactivity against sera from Korean hepatitis C patients in immunoblot analysis. These results suggest that NS5 proteins would be useful as an antigen for detection of antibody against HCV in the blood samples.

• Bulletin of the Korean Chemical Society
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• v.20 no.3
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• pp.301-306
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• 1999

Hepatitis C virus (HCV) has been known to be an enveloped virus with a positive strand RNA genome and the major agent of the vast majority of transfusion associated cases of hepatitis. For viral replication, HCV structural proteins are first processed by host cell signal peptidases and NS2/NS3 site of the nonstructural protein is cleaved by a zinc-dependent protease NS2 with N-terminal NS3. The four remaining junctions are cleaved by a separate NS3 protease. The solution conformations of NS4B/5A, NS5A/5B substrates and NS5A/5B inhibitor have been determined by two-dimensional nuclear magnetic resonance (NMR) spectroscopy. NMR data suggested that the both NS5A/5B substrate and inhibitor appeared to have a folded tum-like conformation not only between P1 and P6 position but also C-terminal region, whereas the NS4B/5A substrate exhibited mostly extended conformation. In addition, we have found that the conformation of the NS5A/5B inhibitor slightly differs from that of NS5A/5B substrate peptide, suggesting different binding mode for NS3 protease. These findings will be of importance for designing efficient inhibitor to suppress HCV processing.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.11
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• pp.4977-4982
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• 2016

Introduction: Elevated serum interleukin (IL) 6 has been reported in patients infected with the hepatitis C virus (HCV), but it remains debatable whether this influences the production of autoantibodies and the biochemical profile of HCV disease. Therefore, this current study was conducted to evaluate the relationship between IL-6 and circulating autoantibody levels in HCV positive patients. Methods: Levels of IL-6 in serum samples from 102 patients with HCV and 103 normal controls were determined by enzyme linked immunosorbent assay (ELISA). Autoantibodies were detected by immunofluorescence. Results: Levels of IL-6 were significantly higher (p=0.028) in patients infected with (HCV) compared with normal group. Autoantibodies were noted in in 43.1% of the patients; of these, 23.5% featured anti-nuclear antibodies (ANA+), 16.7% anti-smooth muscle antibodies (ASMA+), 7.8% anti-mitochondrial antibodies (AMA+), 17.6% anti-parietal cell antibodies (APCA+), 7.8% anti canalicular antibodies, and 2.9% anti reticulin antibodies (ARA+). No patients were found to be positive for anti-brush border antibodies (ABBA) or anti-ribosomal antibodies. (ARiA). No links with IL-6 levels were apparent. Conclusions: IL-6 levels are increased in patients infected with HCV disease and could influence the production of autoantibodies. However, this study did not provide evidence of a specific relationship between IL6 and circulating autoantibodies in such cases.

• Clinical and Experimental Vaccine Research
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• v.12 no.1
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• pp.47-59
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• 2023

Purpose: The development and study of hepatitis C virus (HCV) vaccine candidates' individualized responses are of great importance. Here we report on an HCV DNA vaccine candidate based on selected envelope (E1/E2) epitopes. Besides, we assessed its expression and processing in human peripheral blood mononuclear cells (PBMCs) and in vivo cellular response in mice. Materials and Methods: HCV E1/E2 DNA construct (EC) was designed. The antigen expression of EC was assayed in PBMCs of five HCV-uninfected donors via a real-time quantitative polymerase chain reaction. Serum samples from 20 HCV antibody-positive patients were used to detect each individual PBMCs expressed antigens via enzyme-linked immunosorbent assay. Two groups, five Swiss albino mice each, were immunized with the EC or a control construct. The absolute count of lymph nodes' CD4⁺ and CD8⁺ T-lymphocytes was assessed. Results: Donors' PBMCs showed different levels of EC expression, ranging between 0.83-2.61-fold in four donors, while donor-3 showed 34.53-fold expression. The antigens expressed in PBMCs were significantly reactive to the 20 HCV antibody repertoire (all p=0.0001). All showed comparable reactivity except for donor-3 showing the lowest reactivity level. The absolute count % of the CD4⁺ T-cell significantly increased in four of the five EC-immunized mice compared to the control group (p=0.03). No significant difference in CD8⁺ T-cells % was observed (p=0.89). Conclusion: The inter-individual variation in antigen expression and processing dominance was evident, showing independence in individuals' antigen expression and reactivity levels to antibodies. The described vaccine candidate might result in a promising natural immune response with a possibility of CD4⁺ T-cell early priming.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.1
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• pp.265-270
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• 2015

Hepatocellular carcinoma (HCC) is amongst the top three cancer causes of death worldwide with hepatitis B and C viruses (HBV/HCV) as the main etiological agents. An up-to-date descriptive epidemiology of the burden of HBV/HCV-associated HCC in the Arab world is lacking. We therefore determined the burden of HBV/HCV-associated HCC deaths in the Arab world using the Global Burden of Disease (GBD) 2010 dataset. GBD 2010 provides, for the first time, deaths specifically attributable to viral-associated HCC. We analyzed the data for the 22 Arab countries by age, sex and economic status from 1990 to 2010 and compared the findings to global trends. Our analysis revealed that in 2010, an estimated 752,101 deaths occurred from HCC worldwide. Of these 537,093 (71%) were from HBV/HCV-associated HCC. In the Arab world, 17,638 deaths occurred from HCC of which 13,558 (77%) were HBV/HCV-linked. From 1990 to 2010, the burden of HBV and HCV-associated HCC deaths in the Arab world increased by 137% and 216% respectively, compared to global increases of 62% and 73%. Age-standardized death rates also increased in most of the Arab countries, with the highest rates noted in Mauritania and Egypt. Male gender and low economic status correlated with higher rates. These findings indicate that the burden of HBV/HCV-associated HCC in the Arab world is rising at a much faster rate than rest of the world and urgent public health measures are necessary to abate this trend and diminish the impact on already stretched regional healthcare systems.