• Journal of Microbiology and Biotechnology
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• 제27권7호
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• pp.1336-1344
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• 2017

Hepatitis B virus (HBV) is a major cause of liver cirrhosis and hepatocellular carcinoma. With recent identification of HBV receptor, inhibition of virus entry has become a promising concept in the development of new antiviral drugs. To date, 10 HBV genotypes (A-J) have been defined. We previously generated two murine anti-preS1 monoclonal antibodies (mAbs), KR359 and KR127, that recognize amino acids (aa) 19-26 and 37-45, respectively, in the receptor binding site (aa 13-58, genotype C). Each mAb exhibited virus neutralizing activity in vitro, and a humanized version of KR127 effectively neutralized HBV infection in chimpanzees. In the present study, we constructed a humanized version (HzKR359-1) of KR359 whose antigen binding activity is 4.4-fold higher than that of KR359, as assessed by competitive ELISA, and produced recombinant preS1 antigens (aa 1-60) of different genotypes to investigate the binding capacities of HzKR359-1 and a humanized version (HzKR127-3.2) of KR127 to the 10 HBV genotypes. The results indicate that HzKR359-1 can bind to five genotypes (A, B, C, H, and J), and HzKR127-3.2 can also bind to five genotypes (A, C, D, G, and I). The combination of these two antibodies can bind to eight genotypes (A-D, G-J), and to genotype C additively. Considering that genotypes A-D are common, whereas genotypes E and F are occasionally represented in small patient population, the combination of these two antibodies might block the entry of most virus genotypes and thus broadly neutralize HBV infection.

• 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.

• Journal of Microbiology
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• 제45권5호
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• pp.431-440
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• 2007

A silkworm (Bombyx mori L.) extract known to contain naturally occurring iminosugars, including 1-deoxynojirimycin (1-DNJ) derived from the mulberry tree (Morus alba L.), was evaluated in surrogate HCV and HBV in vitro assays. Antiviral activity of the silkworm extract and one of its purified constituents, 1-DNJ, was demonstrated against bovine viral diarrhea virus (BVDV) and GB virus-B (GBV-B), both members of the Flaviviridae family, and against woodchuck hepatitis virus (WHV) and hepatitis B virus (HBV), both members of the Hepadnaviridae family of viruses. The silkworm extract exhibited a 1,300 fold greater antiviral effect against BVDV in comparison to purified 1-DNJ. Glycoprotein processing of BVDV envelope proteins was disrupted upon treatment with the naturally derived components. The glycosylation of the WHV envelope proteins was affected largely by treatment with the silkworm extract than with purified 1-DNJ as well. The mechanism of action for this therapy may lie in the generation of defective particles that are unable to initiate the next cycle of infection as demonstrated by inhibition of GBV-B in vitro. We postulate that the five constituent iminosugars present in the silkworm extract contribute, in a synergistic manner, toward the antiviral effects observed for the inhibition of intact maturation of hepatitis viral particles and may complement conventional therapies. These results indicate that pre-clinical testing of the natural silkworm extract with regards to the efficacy of treatment against viral hepatitis infections can be evaluated in the respective animal models, in preparation for clinical trials in humans.

• Asian Pacific Journal of Cancer Prevention
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• 제17권7호
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• pp.3381-3384
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• 2016

Background: Hepatitis B virus (HBV) is a key factor for hepatocellular carcinoma (HCC). About 350 million people are affected by chronic infection which is related to the rapid development of liver diseases as well as hepatitis, cirrhosis and hepatocellular carcinoma. Expression of tumor necrosis factor alpha (TNF-${\alpha}$) in the liver demonstrates a major genetic polymorphism which is involved in resistance or susceptibility to chronic HBV infection. Materials and Methods: In this study, two populations were studied by the sequence specific primer-polymerase chain reaction (SSP-PCR) method: HBV cases (n=409), who were HBS-Ag+, and healthy controls (n=483). Results: The results shown that the frequency of TNF-${\alpha}$ -308 G/G genotype in healthy controls (47.2%) was significantly higher than in HBV infected patients (28%) (CI = 1.29-2.61, OR = 1.83, P = 0.0004). Also TNF-${\alpha}$ -308 A/A and A/G genotype frequencies in the healthy controls were 4.6% and 48.2% and in patient group were 19.5% and 52.5% (CI = 2.23-7.12, p: 0.0001, OR: 3.94) respectively. Conclusions: We found that among Iranian people TNF-${\alpha}$ -308A allele not only has the highest genotype frequency but also it has the highest frequency in the world population. In addition, TNF-${\alpha}$-308 G/G polymorphism was associated with HBV resistance, whereas TNF-${\alpha}$-308A (A/A or A/G) polymorphism appeared to associated with chronic HBV infection. These data suggested that among the Iranian population, the -308 G/G polymorphism of TNF-${\alpha}$ gene promoter region has the potential to influence the susceptibility to HBV infection and it may be responsible for viral antigen clearance.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제8권2호
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• pp.202-212
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• 2005

목 적: Transfusion-transmitted virus는 간염과의 연관성이 아직 명확하지 않지만 특정 유전형이 원인불명의 간염 병원체로 작용하거나 다른 간염 바이러스와 중복 감염되어 임상 경과에 영향을 줄 가능성에 대한 연구가 필요하다. 본 연구는 국내 소아 B형 간염, C형 간염 및 원인 불명의 간염 환자의 TTV DNA 양성률과 유전형의 분포를 알아보기 위해 시행하였다. 방 법: 간 기능이 정상인 소아 88명을 대조군으로 하였으며 B형 간염 환자 14명, C형 간염 환아 12명, 2001년 6월부터 2004년 6월까지 인제의대 상계백병원을 방문한 원인 불명의 간염 환자 25명을 대상으로 하였다. 환아의 혈청 검체를 대상으로 N22 시발체를 이용한 PCR과 5'NCR 시발체를 이용한 PCR을 시행하였다. 또한 TLMV DNA 검출을 위한 seminested PCR을 시행 하였다. N22 primer를 이용한 PCR 양성 산물을 대상으로 염기서열의 직접 분석이 시행되었다. 결 과: 1) N22 시발체를 이용한 TTV DNA 양성률은 대조군에서 11.3%, 간염군에서 19.6%였다(p=0.105). B형 간염의 28.5%, C형 간염의 25%, 원인 불명의 간염 24%에서 TTV DNA가 양성이었으며 대조군에 비해 유의한 차이는 없었다. 2) 5'NCR 부위 시발체를 이용한 TTV DNA 양성률은 대조군에서 32.9%, 간염군에서 54.9%였다. B형 간염의 71.4%, C형 간염의 50%, 원인 불명의 간염 48%에서 TTV DNA가 양성이었다. B형 간염 환자군에서 양성률이 대조군에 비해 높았다(p=0.008). 3) 5'NCR 부위 시발체를 이용한 TLMV DNA양성률은 간염 환자군과 정상 대조군에서 각각 29.4% (15/51명), 48.9% (43/88명)였다. B형 간염 21.4% (3/14), C형 간염 16.6% (2/12), 원인 불명의 간염 환자에서 40% (10/25)였다. 4) 염기 서열 분석: N22 시발체를 이용해서 PCR 반응 산물 중 총 29예(간염 환자 8명, 대조군 11명)의 염기서열을 분석한 결과 G1 유전형은 10예(52%)였고 이 중 G1a형이 7예였다. G2 유전형은 3예, G3 유전형은 2예였으며 나머지는 정확한 분류가 되지 않았다. 결 론: 국내 소아에 감염된 TTV 유전형 중 가장 흔한 것은 G1형이었다. TTV DNA 양성률은 대조군과 원인 불명의 간염군 간에 차이는 없었으며, B형 간염군에서 대조군에 비해 높았다.

• IMMUNE NETWORK
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• 제3권4호
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• pp.281-286
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• 2003

Background: Hepatitis B virus (HBV) infection is one of the worldwide public health problem affecting about 300 million people. The envelope protein of HBV consists of three components known as preS1, preS2, and S antigen. According to the recent study, anti-HBs Ab showed effective neutralization ability against HBV from chronic hepatitis B and liver transplant patients, suggesting the possible development of therapeutic antibody. Methods: Spleen cells immunized with S antigen of HBV were fused with myeloma cell line to obtain HBsAg specific monoclonal antibodies. High affinity antibodies against HBsAg (adr, ad and ay type) were selected by competitive ELISA method. Nucleotide sequence of the variable regions of monoclonal antibodies was analyzed by RT-PCR followed by conventional sequencing method. Results: We produced 14 murine monoclonal antibodies which recognize S antigen of HBV. Two of them, A9-11 and C6-9 showed the highest affinity. The sequence analysis of A9-11 revealed that variable regions of the heavy chain and light chains are members of mouse heavy chain I (B) and light chain lambda 1, respectively. Likewise, the sequence analysis of C6-9 revealed that variable regions of the heavy chain and light chains are members of mouse heavy chain II (B) and light chain kappa 1, respectively. Neutralization assay showed that A9-11 and C6-9 effectively neutralize the HBV infection. Conclusion: These results suggest that A9-11 and C6-9 mouse monoclonal antibodies can be used for the development of therapeutic antibody for HBV infection.

• Asian Pacific Journal of Cancer Prevention
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• 제17권2호
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• pp.591-595
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• 2016

The liver is one of the most common sites of cancer in the world, hepatocellular carcinoma (HCC) predominating. Chronic hepatitis B virus infection (CHB) is considered as an important potential risk factors for HCC. Different people have diverse responses to HBV infection regarding the likelihood of HCC development, and host factors such as single nucleotide polymorphisms (SNPs) might account for this. The present study was conducted to evaluate any association between SNP frequencies in two genes, XRCC4 (rs1805377) and ATF6 (rs2070150), and the risk of CHB and HCC development in Thai patients. The study covered 369 subjects including 121 HCC patients, 141 with chronic hepatitis B virus infection (CHB) and 107 healthy controls. With TaqMan real-time PCR, the results showed that no significant association between XRCC4 (rs1805377) and ATF6 (rs2070150) and risk of HCC in the Thai population. From this first study of the 2 polymorphisms and HCC in Thailand it can concluded that rs1805377 and rs2070150 polymorphisms may not be applicable as genetic markers in the Thai population for HCC assessment.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제23권4호
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• pp.311-318
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• 2020

Chronic hepatitis B viral (HBV) infection remains a major health threat, especially in high-prevalence areas. Most infants infected by mother-to-infant HBV transmission become chronic carriers. In Taiwan, many important preventive interventions have been implemented to block the perinatal transmission of HBV in the past 35 years. The first nationwide universal HBV vaccination program was launched in Taiwan in July 1984. The three-dose HBV vaccine completion rate reached 98.1% in 2018. The prevalence of Hepatitis B surface antigen (HBsAg) decreased from 9.8% in pre-vaccinated period in 1984 to 0.5% in the vaccinated cohort in 2014. The incidence of hepatocellular carcinoma in children aged 6-9 years significantly declined from 0.52 to 0.13 per 100,000 children born before and after 1984, respectively. Furthermore, we have performed a maternal HBV screening program during pregnancy since 1984, with the screening rate peaked at 93% in 2012. The HBsAg- and HBeAg-seropositive rate in pregnant women declined from 13.4% and 6.4% in 1984-1985 to 5.9% and 1.0% in 2016, respectively. To closely control perinatal HBV infection, we have administered hepatitis B immunoglobulin immediately after birth and checked the serum level of HBsAg and anti-HBs in high-risk babies born to HBsAg-seropositive mothers, irrespective of their HBeAg status, since July 2019. We have also adopted short-term antiviral treatments such as tenofovir 300 mg daily in the third trimester for highly viremic mothers and reduced the perinatal infection rates from 10.7 to 1.5%. Through all these efforts, we expect to meet the global goal of eliminating HBV infection by 2030.

• IMMUNE NETWORK
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• 제6권1호
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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.

• 대한한의학회지
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• 제30권3호
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• pp.106-110
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• 2009

Objective : To study the Oriental Medicine-based strategies or therapeutics for chronic HBV infection. Methods : A chronic HBV carrier was treated with only oriental therapies. Then, serum biochemical parameters were serially chased, and change of HBV-DNA level was evaluated. Result : The biochemical indicators (AST, ALT, gamma-GTP, bilirubin) fluctuated during the treatment period. After one episode of drastic elevation of serum aminotransferase, HBV-DNA disappeared from the blood along with normalization of biochemical parameters within two years of beginning treatment. Conclusion : Oriental Medicine-based therapeutics could be an alternative strategy against chronic infection of HBV.