• 제목/요약/키워드: HBV polymerase

검색결과 37건 처리시간 0.027초

Structure-Function Analysis of HBV polymerase

  • Cho, Gi-Nam;Na, Seoun-Gon;Jung, Gu-Hung
    • 한국동물학회:학술대회논문집
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    • 한국동물학회 1998년도 한국생물과학협회 학술발표대회
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    • pp.282.1-282
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    • 1998
  • No Abstract, See Full Text

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만성 B형 간질환에서 간염 B virus 표식자 발현에 따른 DNA의 검출 (Detection of Serum Hepatitis B Virus DNA According to HBV Markers in Chronic Hepatitis B Liver Disease)

  • 이동준;최진수;김준환;이헌주
    • Journal of Yeungnam Medical Science
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    • 제14권1호
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    • pp.155-167
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    • 1997
  • 본 연구는, HBV의 증식 및 감염력을 파악하는데 가장 중요한 표지자로 알려진 HBV DNA를 최근 임상에서 많이 이용되고 있는 PCR법을 사용해 검출함으로써 기존의 dot blot법과 PCR법을 비교하고, 만성 간질환 환자에서 HBV의 e항원, 항체체계에 따른 HBV DNA의 검출율을 PCR법을 이용하여 알아봄으로써 HBV의 증식 및 감염력을 파악하고자 무증상 HBsAg 보유자 17명(HBeAg 양성 9명, anti-HBe 양성 8명), 만성 B형 간염 환자 91명(HBeAg 양성 50명, anti-HBe 양성 41명), 간경변증 한자 57명(HBeAg 양성 21명, anti-HBe 양성 36명), 원발성 간세포암 환자 27명(HBeAg 양성 10명, anti­HBe 양성 17명)을 대상으로 HBV DNA의 검출빈도를 조사하여 다음과 같은 결과를 얻었다. Dot blot법의 경우 HBeAg 양성인 환자군, anti-HBe 양성인 환자군에서의 HBV DNA의 검출율은 각각 58.9%, 34.3% 이었고, PCR법에 의한 검출율은 상기군에서 각각 72.2%, 53.9%였다. HBeAg 음성인군에서의 PCR법에 의한 HBV DNA 검출율은 무증상 HBsAg 보유자의 경우 25.0%, 만성 B형 간염 환자군의 경우 61.0%, 간병변증 환자군의 경우 52.8%, 원발성 간세포암 환자군의 경우 52.9%였다. 무증상 HBsAg 보유자에서 HBeAg 양성인 군과 음성인 군간의 HBV DNA 검출율은 각각 77.8%, 25.0%로 유의한 차이가 있었으나, 나머지 군에서는 HBeAg 양성인 군과 음성인 군간의 HBV DNA 검출율의 유의한 차이는 없었다. 이상의 결과로 PCR을 이용할 경우 기존의 dot blot보다 훨씬 예민하게 HBV DNA를 검출할 수 있고, HBsAg 양성인 만성 간질환 환자의 대부분에서는 HBeAg 및 anti-HBe 표식자 체계와는 무관하게 바이러스의 증식이 지속되고 있음을 알 수 있었으며, PCR법이 무증상 HBsAg 보유자의 예후를 알 수 있는 지표로서 유용성에 대한 가능성을 의미하나 확실한 의의를 알기 위하여 전향적인 연구가 필요할 것으로 사료된다.

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Phage Display 기법을 이용한 B형 간염 바이러스 Polymerase의 RNase H 활성을 억제하는 인간 단세포군 항체의 개발 (Development of Human Antibody Inhibiting RNase H Activity of Polymerase of Hepatitis B Virus Using Phage Display Technique)

  • 이성락;송은경;정영주;이영이;김익중;최인학;박세광
    • IMMUNE NETWORK
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    • 제4권1호
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    • pp.16-22
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    • 2004
  • Background: To develop a novel treatment strategy for hepatitis B virus infection, a major cause of liver chirosis and cancer, we aimed to make human monoclonal antibodies inhibiting RNase H activity of P protein playing in important role in HBV replication. In this regard, phage display technology was employed and demonstrated as an efficient cloning method for human monoclonal antibody. So this study analysed the usability of human monoclonal antibody as protein based gene therapy. Methods: RNase H of HBV was expressed as fusion protein with maltose binding protein and purified with amylose resin column. Single chain Fv (scFv) phage antibody library was constructed by PCR cloning using total RNAs of PBMC from 50 healthy volunteers. Binders to RNase H were selected with BIAcore 2000 from the constructed library, and purified as soluble antibody fragment. The affinity and sequences of selected antibody fragments were analyzed with BIAcore and ABI automatic sequencer, respectively. And finally RNase H activity inhibiting assay was carried out. Results: Recombinant RNase H expressed in E. coli exhibited an proper enzyme activity. Naive library of $4.46{\times}10^9cfu$ was screened by BIAcore 2000. Two clones, RN41 and RN56, showed affinity of $4.5{\times}10^{-7}M$ and $1.9{\times}10^{-7}M$, respectively. But RNase H inhibiting activity of RN41 was higher than that of RN56. Conclusion: We cloned human monoclonal antibodies inhibiting RNase H activity of P protein of HBV. These antibodies can be expected to be a good candidate for protein-based antiviral therapy by preventing a replication of HBV if they can be expressed intracellularly in HBV-infected hepatocytes.

Anti-HBc 단독 양성자에서 B형 간염 백신 접종의 면역 반응과 B형 간염 DNA의 조사 (A Study of Immune Response to Hepatitis B Vaccine & HBV DNA in Isolated Anti-HBc Positive Subjects)

  • 김순덕;최지호;김성열;이진수;고희정
    • Journal of Preventive Medicine and Public Health
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    • 제38권2호
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    • pp.170-174
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    • 2005
  • Objectives: The aim of this study was to evaluate the response to a hepatitis B vaccination, and investigate the HBV DNA in subjects with isolated anti-HBc. Methods: 34 subjects with persistent isolated anti-HBc were included in the study. 32 subjects negative for HBsAg, anti-HBs and anti-HBc were included as a control group. They were all vaccinated with Hepaccine at 0, 1 and 2 months, and anti-HBs titers were measured 1 month after the 1st and 3rd vaccinations (1 and 3 months). The HBV-DNA was tested by polymerase chain reaction in subjects with isolated anti-HBc. Results: After the 1st & 3rd vaccinations, the anti-HBs titers$\geq$10mIU/ml were 70.6 & 70.6% in isolated anti-HBc group, and 34.4 & 81.2% in the control group, respectively. There were statistically significant differences after the 1st vaccination, but none after the 3rd, between the two groups. In the isolated anti-HBc and control groups, the primary, amnestic and no responses were 0 vs. 46.9%, 55.9 vs. 6.3% and 29.4 vs. 18.8%, respectively. The HBV DNA was not detected in all subjects with isolated anti-HBc. Conclusion: None of the subjects with isolated anti-HBc had a false positive result (primary response); therefore, they should be excluded from vaccination programs in Korea. To differentiate between immunity and occult infections, a single dose of vaccine, with a follow-up anti-HBs test, is preferable for subjects with isolated anti-HBc. An amnestic response indicates late immunity, and no response a suspect occult infection.

CYP2C19 Genotype Could be a Predictive Factor for Aggressive Manifestations of Hepatocellular Carcinoma Related with Chronic Hepatitis B Infection in Thailand

  • Nun-anan, Pongjarat;Chonprasertsuk, Soonthorn;Siramolpiwat, Sith;Tangaroonsanti, Anupong;Bhanthumkomol, Patommatat;Pornthisarn, Bubpha;Vilaichone, Ratha-korn
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권8호
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    • pp.3253-3256
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    • 2015
  • Background: Chronic hepatitis B virus (HBV) infection related hepatocellular carcinoma (HCC) is a major health problem in the Asia-Pacific region including Thailand. Several factors have been proposed as contributing to hepatocarcinogenesis. This study was aimed to investigate the impact of CYP2C19 genotypic polymorphism in HCC related to chronic HBV infection in Thailand. Materials and Methods: A cross-sectional study was performed between April 2014 and January 2015. Chronic HBV patients with HCC (n=50) and without HCC (n=50) were included. Clinical information and blood samples of all patients were collected. The CYP2C19 genotype was determined by polymerase chain reaction-restriction fragment length polymorphism method, and was classified as rapid metabolizer (RM), intermediate metabolizer (IM) or poor metabolizer (PM). Results: The CYP2C19 genotype frequencies of RM, IM and PM in HBV patients were found to be 19/50 (38%), 25/50 (50%) and 6/50 (12%), respectively. The CYP2C19 genotype frequencies of RM, IM and PM in HBV with HCC patients were 21/50 (42%), 25/50 (50%) and 4/50 (8%), respectively. The distribution of CYP2C19 genotype was not different between patients with and without HCC. Interestingly, among HBV with HCC patients, the RM genotype of CYP2C19 tended to increase risk of aggressive manifestation (OR=2.89, 95%CI=0.76-11.25, P-value=0.07), compared with non RM genotype carriers. Conclusions: CYP2C19 genotype IM was the most common genotype in Thai patients with chronic HBV infection. In addition, genotype RM could be an associated factor for aggressive presentation in HCC related to chronic HBV infection.

Role of IL-18 Gene Promoter Polymorphisms, Serum IL-18 Levels, and Risk of Hepatitis B Virus-related Liver Disease in the Guangxi Zhuang Population: a Retrospective Case-Control Study

  • Lu, Yu;Bao, Jin-Gui;Deng, Yan;Rong, Cheng-Zhi;Liu, Yan-Qiong;Huang, Xiu-Li;Song, Liu-Ying;Li, Shan;Qin, Xue
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권14호
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    • pp.6019-6026
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    • 2015
  • Background: The aim of this study was to assess the relationship between IL-18 gene polymorphisms and HBV-related diseases and whether these polymorphisms influence its expression in the Guangxi Zhuang population. Materials and Methods: We enrolled 129 chronic HBV infected (CHB) patients, 86 HBV-related liver cirrhosis (LC) patients and 160 healthy controls in our study. Polymerase chain reaction-restriction fragment length polymorphism methods were used to detect IL-18 gene -607C/A, -137G/C polymorphisms, and an ELISA kit was employed to determine serum IL-18 levels. Results: No correlation was found between the -607C/A polymorphism and risk of HBV-related disease. For the -137G/C polymorphism, the GC genotype and C allele were associated with a significantly lower risk of CHB (95%CI: 0.32-0.95, p=0.034 and 95%CI: 0.35-0.91, p=0.018) and HBV-related LC (95%CI: 0.24-0.89, p=0.022 and 95%CI: 0.28-0.90, p=0.021). A similar decreased risk was also found with the A-607C-137 haplotype. With respect to IL-18 expression, it was significantly lower in both patient groups, but no association was noted between the two polymorphisms in the IL-18 gene and its expression. Conclusions: Our study indicated that the -137C allele in the IL-18 gene may be a protective factor for HBV-related disease, and serum IL-18 level may be inversely associated with CHB and HBV-related LC.

Associations Between Three Common MicroRNA Polymorphisms and Hepatocellular Carcinoma Risk in Chinese

  • Hao, Yu-Xia;Wang, Jun-Ping;Zhao, Long-Feng
    • Asian Pacific Journal of Cancer Prevention
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    • 제14권11호
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    • pp.6601-6604
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    • 2013
  • Aim: Associations between polymorphisms in miR-146aG>C, miR-196a2C>T and miR-499A>G and risk of HCC, and interaction with HBV infection in a Chinese population, were the target of the present research. Methods: The duplex polymerase-chain-reaction with confronting-two-pair primers (PCR-RFLP) was performed to determine the genotypes of the miR-146aG>C, miR-196a2C>T and miR-499A>G genotypes. Associations of polymorphisms with the risk of HCC were estimated by conditional logistic regression analysis. Results: Drinking, family history of cancer, HBsAg and HCV were risk factors for HCC. Multivariate regression analyses showed that subjects carrying the miR-196a2 CC genotype had significantly increased risk of HCC, with an adjusted OR (95% CI) of 2.18 (1.23-3.80). In addition, cases carrying the miR-196a2 C allele had a 1.64-fold increase in the risk for HCC (95%CI=1.03-2.49). The miR-196a2 CT and TT genotypes greatly significantly increased the risk of HCC in subjects with HBV infection, with adjusted ORs (95% CI) of 2.02 (1.12-3.68) and 2.69 (1.28-5.71), respectively. Conclusion: Our results demonstrate that miR-196a2 CC genotype and C allele have an important role in HCC risk in Chinese, especially in patients with HBV infection.

Association of Viral Infections with Risk of Human Lymphomas, Egypt

  • Kadry, Dalia Y;Khorshed, Amira M;Rashed, Reham A;Mokhtar, Nadia M
    • Asian Pacific Journal of Cancer Prevention
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    • 제17권4호
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    • pp.1705-1712
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    • 2016
  • Background: The aim of this study was to determine and evaluate the association of different viral infections, with hepatitis B and C viruses, Epstein-Barr virus, cytomegalovirus and human herpes virus-8 (HBV, HCV, EBV, CMV, HHV-8) with the risk of lymphomas (Hodgkin and non-Hodgkin) among Egyptian patients, and correlate with the histopathological staging and typing as well as the prevalence of combined infections. Materials and Methods: A total of 100 newly diagnosed lymphoma patients with 100 healthy age and sex matched normal controls were assayed for viral infection using enzyme linked immunosorbant assay (ELISA) followed by real time polymerase chain reaction (RT-PCR). Results: Our results showed a high statistical significant difference between cases and controls as regards clinical and laboratory findings (P<0.001 and=0.003). A high statistical difference was seen for the association of most viruses and lymphoma cases (p<0.001) except for positive HBs Ag, positive CMV IgG and HHV-8 (p=0.37, 0.70 and 1.0 respectively). No statistical significant difference was found between Hodgkin (HL) and non-Hodgkin (NHL) as regards viral prevalence except HCV antigen, 57.1% for HL and 26.5% for NHL (p = 0.03). Only, HBV DNA showed a high significant value among infiltrated bone marrow cases (p=0.003) and finally, a high significant association of 2 combined viral infections with infiltrated bone marrow lymphoma cases (p=0.04). Conclusions: Our results showed that infection with HBV, HCV, CMV and EBV were associated with increased risk of lymphoma among the Egyptian population. Detection of new associations between infectious agents and risk of cancer development will facilitate progress in elaboration of prophylactic measures, early diagnostic methods and, hopefully, novel therapy of malignant tumours.

Cyclophilin A as a New Therapeutic Target for Hepatitis C Virus-induced Hepatocellular Carcinoma

  • Lee, Jinhwa
    • The Korean Journal of Physiology and Pharmacology
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    • 제17권5호
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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.