• Korean Journal of Microbiology
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• 제49권3호
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• pp.221-227
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• 2013

Human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) cause viral infections that lead to chronic diseases. When they invade human body, virus specific T cells play an important role in antiviral effector functions including killing virus-infected cells and helping B cells to produce specific antibodies against viral proteins. The antiviral activity of T cells is usually affected by immune-regulatory factors that express on surface of T cells. Recently, many researchers have investigated the relationship between effector functions of virus specific T cells and characteristics of immune regulatory factors (e.g., CD28, CD25, CD45RO, FoxP3, PD-1, CTLA-4). In particular, Immune inhibitory molecules such as forkhead box P3 (FoxP3), programmed death-1 (PD-1), and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) are associated with T-cell dysfunction. They are shown to be up-regulated in chronic viral diseases such as hepatitis B, hepatitis C or human immunodeficiency virus infection. Therefore, the positive correlation between viral persistence and expression of immune regulatory factors (FoxP3, PD-1, and CTLA-4) has been suggested. In this review, the roles of immune regulatory factors FoxP3, PD-1, and CTLA-4 were discussed in chronic viral diseases such as HIV, HBV, or HCV.

• The Journal of Korean Society of Virology
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• 제27권1호
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• pp.9-17
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• 1997

Hepatitis C virus (HCV) E2 protein is known to be one of putative envelope proteins. To develop a sensitive detection method for HCV infected tissues and cells, monoclonal antibodys (MAbs) to the E2 protein of HCV were prepared from mice immunized with recombinant baculovirus-expressing E2 protein (Bac-E2). Several hybridoma clones secreting various levels of MAb were isolated and isotypes of these MAb were determined. One clone (L.2.3.3) was used for ascites production and the E2-MAb was purified and characterized. The L.2.3.3 reacted well with both Bac-E2 and E. coli expressed glutathione-S-transferase-E2 (GST-E2) fusion proteins. Using HCV patient sera, E2 envelope protein was found to be localized in the cell membrane boundary both in CHO cells and insect cells which express HCV E2 protein. Similar result was obtained when same cells were treated with the MAb L.2.3.3. These results demonstrated that Bac-E2 protein is capable of eliciting high titer antibody production in mice.

• Biomolecules & Therapeutics
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• 제17권2호
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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.

• Journal of Microbiology
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• 제37권2호
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• pp.90-96
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• 1999

The core protein of the hepatitis C virus (HCV) is a multifunctional protein. The HCV core protein was reported to regulate cellular gene expression and transform primary rat embryo fibroblast cells. However, the role of the core protein in the pathogenesis of HCV-associated liver diseases is not well understood. To investigate the functional role of the core protein in cytophathogenicity, we have constructed stable expression systems of full length or truncated HCV core protein lacking the C-terminal hyderophobic domains and established HepG2 cell clones constitutively expressing the core protein. The full length core protein was localized in the cytoplasm and the C-terminal truncated core protein was localized in the nucleus. HepG2 cells expressing nuclear, truncated core protein showed elevated cell death during cultivation compared to untransfected cells and full length core-expressing cells. In the treatment with bleomycin, both cell clones expressing full length or truncated core protein appeared to be more sensitive to blemoycin than the parental HepG2 cells. These results suggest that the core protein may play a role in HCV pathogenesis promoting apoptotic cell death of infected cells.

• Korean Journal of Microbiology
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• 제43권3호
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• pp.159-165
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• 2007

For the development of basic genetic materials for specific and effective therapeutic approach to suppress multiplication of hepatitis C virus (HCV), HCV internal ribosome entry site (IRES)-targeting hammerhead ribozyme which activity is allosterically regulated by HCV regulatory protein, NS5B RNA replicase, was developed. The ribozyme targeted most effectively to +382 nucleotide (nt) site of HCV IRES RNA. The allosteric ribozyme was designed to be composed of sequence of RNA aptamer to HCV NS5B, communication module sequence which can transfer structural transition for inducing ribozyme activity upon binding NS5B to the aptamer, and sequence of ribozyme targeting +382 nt of HCV IRES. Noticeably, we employed in vitro selection technology to identify the most appropriate communication module sequence which can induce ribozyme activity depending on the US5B protein. We demonstrated that the ribozyme was nonfunctional either in the absence of any proteins or in the presence of control bovine serum albumin. In sharp contrast, the allosteric ribozyme can induce activity of cleavage reaction with HCV IRES RNA in the presence of the HCV NS5B protein. This allosteric ribozyme can be used as lead compound for specific and effective anti-HCV agent, tool for highthroughput screening to isolate lead chemicals for HCV therapeutics, and ligand for biosensor system for HCV diagnosis.

• Bulletin of the Korean Chemical Society
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• 제31권6호
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• pp.1643-1648
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• 2010

Adenosine 5'-phosphonates have been reported as potential chain terminators against Hepatitis C virus (HCV); therefore, we developed convenient sequences for synthesis of modified adenosine 5'-phosphonates in which the hydroxyl group at 2' or 3'-position of the sugar moiety is substituted with the azido or amino group and the oxymethyl group at the 4'-position is modified by the ethylene or vinyl group. This synthetic sequence can provide six adenosine 5'-phosphonates via one protocol, and is considered to be very efficient and a convenient route of synthesis. An assay of adenosine 5'-phosphonate analogues (1, 2, 3, 4, 5, and 6) against HCV infection is now in progress.

• Asian Pacific Journal of Cancer Prevention
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• 제13권8호
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• pp.3663-3667
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• 2012

The hepatitis B virus (HBV) and the hepatitis C virus (HCV) are still public health problems in Yemen, with older individuals having much higher prevalence than younger generations. However, research on the prevalence of viral hepatitis in association with hepatocellular cancer (HCC) has not yet been undertaken in Yemen. The aim of this study was to determine the prevalence of HBV and HCV infection among HCC patients and to estimate the risk of these infections being associated with the development of HCC. A cross-sectional study was conducted on patients attending oncology outpatient in Sana'a, Yemen, through the period 2008-mid 2010 with confirmed diagnosis of HCC. A total of 88 cases were studied thoroughly with different investigations such as CT-scan, ultrasound, tumour marker, alpha-feto-protein and histopathological biopsy. A structured questionnaire was also applied and physical examination done to assess the general condition of the patients. Statistical package (SPSS version 16) was used for analysis of the data. The mean age of the cases was 61.2 years (${\pm}12.6$) with half over 60 years. There were fewer male patients (36%) compared to females and most (97%) only had basic /no formal education. Seventy nine (89%) were diagnosed as HCC cases with histopathological biopsy while the rest were diagnosed by ultrasound, CT scan, tumour marker, and alpha-feto-protein. Around one-third of the subjects were positive for HBsAg and HCV antibodies. Multivariate analysis showed infection with HCV and use of smoking was associated with HCC diagnosis. Although an association was observed between the occurrence of HCC and viral hepatitis (either HBV or HCV) and cigarette smoking, but the rate of viral infection was lower than what has been reported elsewhere.

• Journal of Life Science
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• 제17권6호통권86호
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• pp.766-771
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• 2007

The co-infection with hepatitis B virus (HBV) and hepatitis C Virus (HCV) is associated with a more severe liver disease and increased frequency in the development of hepatocellular carcinoma com-pared to those with single infection. Here, we demonstrated that HBV X protein (HBx) and HCV Core cooperatively up-regulated the level of p53 in human hepatoma HepG2 cells. The elevated p53 subsequently stimulated the expression of proapoptotic Bax whereas it repressed the expression of antiapoptotic Bcl2. These effects, however, were not observed in p53-negative Hep3B cells. Consistently to their cooperative regulation of apoptotic effectors, HBx and HCV Core additively stimulated cisplatin-mediated apoptotic cell death of HepG2 but not of Hep3B cells. These results may help to explain the development of a more severe liver disease in patients co-infection with HBV and HCV as well as some contradictory results on the roles of HBx and Core in apoptosis.

• Asian Pacific Journal of Cancer Prevention
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• 제15권18호
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• pp.7725-7730
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• 2014

Hepatocellular carcinoma (HCC) is the third most common cause for cancer death in the world, now being especially linked to chronic hepatitis C virus (HCV) infection. This case-control study consisting of 65 HCC patients and 82 patients with other malignant tumours as controls was conducted to determine the association of HCV markers with HCC. Serum of each participant was obtained for detection of HCV Ab and RNA by DNA enzyme immunoassay (DEIA). Twenty six per cent (26.0%) of HCC patients had positive anti-HCV which was significantly greater than the control group (p=0.001). HCC patients significantly have a risk of exposure to HCV infection almost 3 times than the control group (OR=2.87, 95% C.I=1.1-7). Anti-HCV seropositive rate was significantly (p=0.03) higher among old age HCC patients and increases with age. Males with HCC significantly showed to have more than 9 times risk of exposure to HCV infection (OR=9.375, 95 % CI=1.299-67.647) than females. HCV-RNA seropositive rate was (70.8%) significantly higher among HCC patients compared to (22.2%) the control group (p=0.019). The most prevalent genotype (as a single or mixed pattern of infection) was HCV-1b. This study detected a significantly higher HCV seropositive rate of antibodies and RNA in HCC patients.

• Journal of Preventive Medicine and Public Health
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• 제55권3호
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• pp.263-272
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• 2022

Objectives: Infections with hepatitis B, C, and D virus (HBV, HCV, and HDV) are a major public health problem and lead to serious complications such as cirrhosis and hepatocellular carcinoma. We aimed to determine the seroprevalence of hepatitis B surface antigen (HBsAg), anti-HCV, anti-HDV immunoglobulin G, alpha-fetoprotein (AFP), and dual and triple hepatitis virus infections in Mongolia. Methods: A total of 2313 participants from urban and rural regions were randomly recruited for this cross-sectional study. A questionnaire was used to identify the risk factors for hepatitis virus infections, and the seromarkers were measured using immunoassay kits. Results: Among all participants, the prevalence of HBV, HCV, and HDV was 15.6%, 36.6%, and 14.3%, respectively. The infection rates were significantly higher in females and participants with a lower education level, rural residence, older age, and a history of blood transfusion. HBV and HCV co-infection was found in 120 (5.2%) participants and HBV, HCV, and HDV triple infection was detected in 67 (2.9%) participants. The prevalence of elevated AFP was 2.7%, 5.5%, and 2.6% higher in participants who were seropositive for HBsAg (p=0.01), anti-HCV (p<0.001), and anti-HDV (p=0.022), respectively. Elevated AFP was more prevalent in participants co-infected with HBV and HCV (5.8%, p=0.023), HBV and HDV (6.0%, p<0.001), and triple-infected with HBV, HCV, and HDV (7.5%) than in uninfected individuals. Conclusions: Nearly half (49.8%) of the study population aged ≥40 years were infected with HBV, HCV, or HDV, and 22.4% had dual or triple infections.