• BMB Reports
• /
• v.37 no.6
• /
• pp.741-748
• /
• 2004

The hepatitis C virus is associated with the development of liver cirrhosis and hepatocellular carcinomas. Among the 10 polyproteins produced by the virus, no function has been clearly assigned to the non-structural 5A (NS5A) protein. This study was designed to identify the hepatocellular proteins that interact with NS5A of the HCV. Yeast two-hybrid experiments were performed with a human liver cDNA prey-library, using five different NS5A derivatives as baits, the full-length NS5A (NS5A-F, amino acid (aa) 1~447) and its four different derivatives, denoted as NS5A-A (aa 1~150), -B (aa 1~300), -C (aa 300~447) and D (aa 150~447). NS5A-F, NS5A-B and NS5A-C gave two, two and 10 candidate clones, respectively, including an AHNAK-related protein, the secreted frizzled-related protein 4 (SFRP4), the N-myc downstream regulated gene 1 (NDRG1), the cellular retinoic acid binding protein 1 (CRABP-1), ferritin heavy chain (FTH1), translokin, tumor-associated calcium signal transducer 2 (TACSTD2), phosphatidylinositol 4-kinase (PI4K) and $centaurin{\delta}$ 2 ($CENT{\delta}2$). However, NS5A-A produced no candidates and NS5A-D was not suitable as bait due to transcriptional activity. Based on an in vitro binding assay, CRABP-1, PI4K, $CENT{\delta}2$ and two unknown fusion proteins with maltose binding protein (MBP), were confirmed to interact with the glutathione S-transferase (GST)/NS5A fusion protein. Furthermore, the interactions of CRABP-1, PI4K and $CENT{\delta}2$ were not related to the PXXP motif (class II), as judged by a domain analysis. While their biological relevance is under investigation, the results contribute to a better understanding of the possible role of NS5A in hepatocellular signaling pathways.

• 대한예방의학회:학술대회논문집
• /
• 1999.10a
• /
• pp.1-15
• /
• 1999

In a case-control study to evaluate the factors involved in the development of hepatocellular carcinoma, polymorphisms of the p53 gene were compared in 68 cases mostly infected with hepatitis C virus (HCV) and 68 controls matched for sex and age: DNA from peripheral blood leukocytes was analyzed by the polymerase chain reaction-single strand conformation polymorphism method and direct sequencing. Polymorphisms analyzed were those in exon 4 (CCC vs. CGC, Pro vs. Arg at codon 72, Al allele vs. A2 allele), intron 2 (C vs. G at nucleotide 38, Al vs. A2), intron 3 (C vs. A at nucleotide 65, Al vs. A2; absence and presence of 16 base pair repeat at nucleotides 24 to 39, Al vs. A2), intron 6 (A vs. G at nucleotide 62, Al vs. A2) and intron 7 (C and T vs. T and G at nucleotides 72 and 92, Al vs. A2). A significantly higher frequency of the allele for CCC (Pro, Al) at codon 72 of exon 4 was found in cases (39%) than in controls (26%) (p<0.05). Highly significant linkage of the polymorphisms in exon 4, intron 2, intron 3 and intron 7, and between the intron 3-16 bp duplication and polymorphism in intron 6 also was found. Matched Fair analysis showed significantly higher frequencies of certain haplotypes (1-1-1-1-2-2 or 1-1-2-1-2-1 for exon 4, intron 2, intron 3, the intron 3-16 bp duplication, intron 6 and intron 7) in cases than in controls (p=0.014, OR=2.27, 95% CI= 1.08-5.12). No preference of specific p53 polymorphisms for specific HCV genotype was detected. These findings suggest that in hepatocarcinogenesis mainly due to HCV infection, genetic factors may be involved and that genetic markers can serve as predictors of a high-risk group for hepatocarcinogenesis.

• Pediatric Gastroenterology, Hepatology & Nutrition
• /
• v.8 no.1
• /
• pp.41-48
• /
• 2005

Purpose: Non-A, B, C viral hepatitis is the name given to the disease with clinical viral hepatitis, but in which serologic evidence of A, B, C hepatitis has not been found. Little is known about the etiology and clinical features of non-A, B, C viral hepatitis in children. Methods: A clinical analysis of 45 cases with non-A, B, C viral hepatitis who were admitted to the Department of Pediatrics, Pusan National University Hospital, from January 2001 to June 2004 was carried out retrospectively. Patients who were positive for HBsAg, anti-HAV and anti-HCV and had toxic, metabolic, autoimmune, or neonatal hepatitis were excluded in this study. Results: Among 45 cases of non-A, B, C viral hepatitis, the etiology was unknown in 26 (57.8%), CMV (cytomegalovirus) in 14 (31.1%), EBV (Epstein Barr virus) in 2 (4.4%), HSV (herpes simplex virus) in 2 (4.4%) and RV (rubella virus) in 1 (2.2%). Twenty seven out of 45 (60.0%) patients were under 1 year of age. Sixteen (33.3%) patients had no specific clinical symptoms and were diagnosed incidentally. On physical examination, twenty seven out of 45 patients (60.0%) had no abnormal findings. Forty three out of 45 patients (95.6%) showed classic clinical course of acute viral hepatitis, whereas fulminant hepatitis developed in two patients. Mean serum ALT (alanine aminotransferase) level was $448.7{\pm}771.9IU/L$. Serum ALT level was normalized in 31 out of 45 patients (81.6%) within 6 months and all patients within 18 months. Aplastic anemia was complicated in a case. Conclusion: Although most patients with non-A, B, C viral hepatitis showed a good prognosis, a careful follow-up would be necessary because some of them had a clinical course of chronic hepatitis, fulminant hepatitis and severe complication such as aplastic anemia.

• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.4
• /
• pp.2093-2097
• /
• 2016

Background: HCV is a major global health problem. IL-27 is a member of the IL-6/IL-12 cytokine family with a broad range of anti-inflammatory properties. Recent studies highlighted the effect of a SNP in the IL-27 promoter region on modulating the progression of infectious diseases and individual responses to therapy. Aim of the work: The present study investigated the potential role of (-964 A/G) SNP in the promoter region of IL-27p28 gene (alleles rs153109) on the outcome of HCV infection among genotype 4a infected patients. Materials and Methods: HCV genotyping confirmed that all of the HCV-infected patients had genotype 4a infection. Genomic DNA was extracted from 111 patients with chronic HCV infection, 42 spontaneous resolvers (SR) and 16 healthy controls. IL- 27p28.rs153109 genotyping was assessed using PCR-RFLP then confirmed by DNA sequencing. Results: The frequency of IL-27-p28.rs153109AA, AG, and GG genotypes among chronically infected subjects were 74.8 %, 25.2%, and 0% while among the SR, they were 57.1%, 35.7%, and 7.14%, respectively. Our data show the unique presence of G/G genotype in the SR group (3 patients; 7.14%). Moreover, the "G" allele frequencies among chronic and resolved subjects were 12.6% and 25.0%, respectively (p=0.0136). Importantly, subjects with the GG genotype were more likely to clear their HCV infection than those with the AA genotype (p=0.0118). Conclusions: HCV genotype 4a subjects with the IL-27-p28.rs153109 A/G and G/G genotype were more likely to clear their HCV infection. Therefore, we propose IL- 27p28.rs153109SNPas a genetic biomarker for predicting HCV infection outcome.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.12
• /
• pp.7251-7256
• /
• 2013

Objectives: To estimate the proportion of liver cancer cases and deaths due to infection with hepatitis B virus (HBV), hepatitis C virus (HCV), aflatoxin exposure, alcohol drinking and smoking in China in 2005. Study design: Systemic assessment of the burden of five modifiable risk factors on the occurrence of liver cancer in China using the population attributable fraction. Methods: We estimated the population attributable fraction of liver cancer caused by five modifiable risk factors using the prevalence data around 1990 and data on relative risks from meta-analyses, and large-scale observational studies. Liver cancer mortality data were from the 3rd National Death Causes Survey, and data on liver cancer incidence were estimated from the mortality data from cancer registries in China and a mortality/incidence ratio calculated. Results: We estimated that HBV infection was responsible for 65.9% of liver cancer deaths in men and 58.4% in women, while HCV was responsible for 27.3% and 28.6% respectively. The fraction of liver cancer deaths attributable to aflatoxin was estimated to be 25.0% for both men and women. Alcohol drinking was responsible for 23.4% of liver cancer deaths in men and 2.2% in women. Smoking was responsible for 18.7% and 1.0%. Overall, 86% of liver cancer mortality and incidence (88% in men and 78% in women) was attributable to these five modifiable risk factors. Conclusions: HBV, HCV, aflatoxin, alcohol drinking and tobacco smoking were responsible for 86% of liver cancer mortality and incidence in China in 2005. Our findings provide useful data for developing guidelines for liver cancer prevention and control in China and other developing countries.

• IMMUNE NETWORK
• /
• v.13 no.1
• /
• pp.25-29
• /
• 2013

Ribavirin is an antiviral drug used in combination with pegylated interferon-${\alpha}$ (IFN-${\alpha}$) for the treatment of hepatitis C virus (HCV) infection. Recently, ribavirin was reported to inhibit the suppressive activity of regulatory T (Treg) cells. In the present study, we re-evaluated the effect of ribavirin on $CD4^+$ $CD4^+$ $CD25^+$ Treg cells from normal donors. First, we examined the expression of CTLA-4 and CD39, which are known to play a role in the suppressive function of Treg cells. We found that ribavirin treatment did not modulate the expression of CTLA-4 and CD39 in Treg cells. We also studied the effect of ribavirin on Treg cells in the presence of IFN-${\alpha}$; however, the expression of CTLA-4 and CD39 in Treg cells was not changed by ribavirin in the presence of IFN-${\alpha}$. Next, we directly evaluated the effect of ribavirin on the suppressive activity of Treg cells in the standard Treg suppression assay, by co-culturing CFSE-labeled non-Treg $CD4^+$ T cells with purified Treg cells. We found that ribavirin did not attenuate the suppressive activity of Treg cells. Taken together, while ribavirin reversed Treg cell-mediated suppression of effector T cells in the previous study, we herein demonstrate that ribavirin does not impair the suppressive activity of Treg cells.

• BMB Reports
• /
• v.44 no.9
• /
• pp.607-612
• /
• 2011

Several investigators have shown that CpG-DNA has outstanding effects as a Th1-responsive adjuvant and that its potent adjuvant effects are enhanced by encapsulation with a liposome of proper composition. In this study, we showed that encapsulation with phosphatidyl-${\beta}$-oleoyl-${\gamma}$-palmitoyl ethanolamine (DOPE): cholesterol hemisuccinate (CHEMS) complex enhances the immunostimulatory activity of CpG DNA and the binding of CpG-DNA to TLR9. We also examined involvement of myeloid differentiation protein (MyD88) and NF-${\kappa}B$ activation in liposome-encapsulated CpG-DNA-induced IL-8 promoter activation. In this manuscript, the natural phosphodiester bond CpG-DNA encapsulated by DOPE : CHEMS complex is designated as Lipoplex(O). Importantly, we successfully screened B cell epitopes of envelope protein (E protein) of hepatitis C virus (HCV-E) and attachment glycoprotein G of human respiratory syncytial virus (HRSV-G) by immunization with complexes of several peptides and Lipoplex(O) without carriers. Therefore, Lipoplex(O) is potentially applicable as a universal adjuvant for peptide-based epitope screening and antibody production.

• Journal of Preventive Medicine and Public Health
• /
• v.37 no.4
• /
• pp.337-344
• /
• 2004

Objectives : This study was performed to determine the incidence density and the prevalence of sero-positive hepatitis C from 1999 to 2002 among adults aged 20 and over residing in Seoul and the Gyeonggi province. Method : The data for period was obtained from 114,635 adults, residing in Seoul or the Gyeonggi province, who had undertaken comprehensive health screening tests from Jan 1999 to Dec 2002 in a University hospital in Seoul. Among them, subjects with sero-negative status against hepatitis C were selected (21,408 in 1999, 28,830 in 2000) and then followed up until Dec 2002 to determine the incidence of hepatitis C during this period. The serum was tested with the immunoradiometric assay (IRMA) which uses third generation HCV antibody. Age adjusted rates were estimated by direct standardization using a reference population of 2000 aged from 20 to 80 years. Results : The prevalence of anti-HCV from 1999 to 2002 was 2.1 per 1000 persons(95% CI $1.8{\sim}2.4$). Male showed 1.7 per 1000 persons (95% CI $1.4{\sim}2.1$), while female showed 2.7 per 1000 persons(95% CI $2.2{\sim}3.2$). Age?sex adjusted rate showed 2.8 per 1000 persons (95% CI $2.64{\sim}2.96$), which is lower than the results of some previous study. The prevalence showed a significantly increasing pattern with age both in males and females (p<0.05). The incidence density of anti-HCV among the population aged 20 and over was 1.1 per 104 person-years at risk (95% CI $0.6{\sim}2.4$); 1.2 (95% CI $0.6{\sim}2.7$) for males and 0.8 (95% CI $0.6{\sim}4.2$) for females. Age adjusted incidence density was 2.91 per 104 person-years at risk (95% CI $2.43{\sim}3.38$) for those aged 20 and over. It showed an increasing pattern with age (p<0.05), especially for those age over 50 years. Conclusion : The study subjects for this study were supposedly healthier than the general population so the prevalence and incidence for the general population are thought to be higher than the results of the present study.

• Anatomy and Cell Biology
• /
• v.56 no.4
• /
• pp.526-537
• /
• 2023

Hepatitis C virus (HCV) infection is a major health problem worldwide and its eradication is mandatory. Direct acting HCV polymerase inhibitors, such as Sofosbuvir (SOF), is an effective regimen. However, it has some side effects like mutagenesis, carcinogenesis, and the impairment of testicular function. It is important to evaluate the safety of SOF on the ovary, as there are no studies yet. Increasing the production of Reactive Oxygen Species (ROS), causes oxidative stress, which affects ovulation process, female reproduction, and fertility. Accumulation of SOF in the cells was demonstrated to promote ROS generation. Vitamin E (Vit E) is an antioxidant agent that has an essential role in the female reproductive system, its deficiency can cause infertility. We explored the effect of SOF treatment alone and co-treated with Vit E on ovarian ROS level and ovarian morphology experimentally using biochemical and immunohistochemical studies. Significant changes in oxidative stress markers; nitric oxide and malondialdehyde lipid peroxidation, antioxidant enzymes; catalase, super oxide dismutase, and reduced glutathione, proliferating markers; proliferation cell nuclear antigen and Ki-67 antigen and caspase 3 apoptotic marker were demonstrated. It was shown that where SOF induced oxidative stress, it also aggravated ovarian dysfunction. The essential role of Vit E as an antioxidant agent in protecting the ovarian tissue from the effect of oxidative stress markers and preserving its function was also displayed. This could be guidance to add Vit E supplements to SOF regimens to limit its injurious effect on ovarian function.

• Korean Journal of Clinical Laboratory Science
• /
• v.54 no.1
• /
• pp.28-37
• /
• 2022

Pregnancy requires an important interpretation of thyroid function tests. The presence of anti-thyroid antibodies and viral infectious agents affect the health of both the fetus and the mother. Hence, a selective evaluation of thyroid function in pregnancy is required. This study is a retrospective cross-sectional survey to examine the correlation between thyroid hormones and viral infections during pregnancy. The results showed that the triiodothyronine (T3) decreased with increasing age, especially in the hepatitis C virus (HCV)-positive group (P<0.01). In addition, although negative for the human immunodeficiency virus (HIV), thyroxine (FT4) showed a significant increase in near-threshold or twin pregnant women (P<0.05). The thyroid stimulating hormone (TSH) was highly distributed at the age of 30, and there was no statistically significant correlation with other viral infection factors. In addition, as a result of dividing and analyzing the result of TSH by the quantiles, FT4 and T3 showed a positive correlation but showed a negative correlation with TSH (P<0.05). Therefore, the evaluation of prenatal thyroid screening during pregnancy and viral infection factors should reflect the time of pregnancy, exposure to infection, and the quantitative values. Adequate thyroid hormone and viral infections availability is important for an uncomplicated pregnancy and optimal fetal development.