• Molecules and Cells
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• 제42권1호
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• pp.67-78
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• 2019

Methylation of HBV cccDNA has been detected in vivo and in vitro; however, the mechanism and its effects on HBV replication remain unclear. HBx derived from a 1.2-mer HBV replicon upregulated protein levels and enzyme activities of DNA methyltransferase 1 (DNMT1), 3a, and 3b, resulting in methylation of the negative regulatory region (NRE) in cccDNA, while none of these effects were observed with an HBx-null mutant. The HBx-positive HBV cccDNA expressed higher levels of HBc and produced about 4-fold higher levels of HBV particles than those from the HBx-null counterpart. For these effects, HBx interrupted the action of NRE binding protein via methylation of the C-1619 within NRE, resulting in activation of the core promoter. Treatment with 5-Aza-2′dC or DNMT1 knock-down drastically impaired the ability of HBx to activate the core promoter and stimulate HBV replication in 1.2-mer HBV replicon and in vitro infection systems, indicating the positive role of HBx-mediated cccDNA methylation in HBV replication.

• Asian Pacific Journal of Cancer Prevention
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• 제16권18호
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• pp.8665-8670
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• 2016

Background and Aims: Hepatitis B virus (HBV) reactivation was reported to be induced by transcatheter arterial chemoembolization (TACE) in HBV-related hepatocellular carcinonma (HCC) patients with a high incidence. The effective strategy to reduce hepatitis flares due to HBV reactivation in this specific group of patients was limited to lamivudine. This retrospective study was aimed to investigate the efficacy of prophylactic entecavir in HCC patients receiving TACE. Methods: A consecutive series of 191 HBV-related HCC patients receiving TACE were analyzed including 44 patients received prophylactic entecavir. Virologic events, defined as an increase in serum HBV DNA level to more than 1 log10 copies/ml higher than nadir the level, and hepatitis flares due to HBV reactivation were the main endpoints. Results: Patients with or without prophylactic were similar in host factors and the majorities of characteristics regarding to tumor factors, HBV status, liver function and LMR. Notably, cycles of TACE were parallel between the groups. Ten (22.7%) patients receiving prophylactic entecavir reached virologic response. The patients receiving prophylactic entecavir presented significantly reduced virologic events (6.8% vs 54.4%, p=0.000) and hepatitis flares due to HBV reactivation (0.0% vs 11.6%, p=0.039) compared with patients without prophylaxis. Kaplan-Meier analysis illustrated that the patients in the entecavir group presented significantly improved virologic events free survival (p=0.000) and hepatitis flare free survival (p=0.017). Female and Eastern Cooperative Oncology Group (ECOG) performance status 2 was the only significant predictors for virological events in patients without prophylactic antiviral. Rescue antiviral therapy did not reduce the incidence of hepatitis flares due to HBV reactivation. Conclusion: Prophylactic entecavir presented promising efficacy in HBV-related cancer patients receiving TACE. Lower performance status and female gender might be the predictors for HBV reactivation in these patients.

• Journal of Microbiology and Biotechnology
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• 제18권10호
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• pp.1722-1728
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• 2008

The natural course of chronic hepatitis B (CH-B) virus infection is reportedly variable, and the long-term outcomes in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B infection are distinct from HBeAg-positive chronic hepatitis. However, the molecular virological factors that contribute to the progression of liver disease in the south Indian setting remain largely unclear. We prospectively studied 679 consecutive patients for HBsAg, HBeAg, anti-HBe, and HBV DNA by qualitative PCR. Randomly selected samples were subjected to bidirectional sequencing to reveal core/precore variants. Of the total 679 chronic HBV cases investigated, 23% (154/679) were replicative HBV carriers. Furthermore, amongst the 560 HBV DNA samples analyzed, 26% (146/560) were viremic. Among the 154 HBeAg positive cases, HBV DNA was positive in 118 cases (77%), significantly (p<0.001) higher than the anti-HBe positive (7%) (28/406) cases. Significant increase in liver disease (p<0.01) with ALT enzyme elevation (p<0.001) was observed in both HBe and anti-HBe viremic cases. Interestingly, low frequencies of mutations were seen in the precore region of the HBV strains studied. HBV precore and core promoter variants were less often detected in subjects with "e" negative chronic HBV infection and, therefore, may not have a prognostic role in determining liver disease sequelae in this part of tropical India.

• Biomolecules & Therapeutics
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• 제6권2호
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• pp.139-144
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• 1998

Abstract -Phyllanthus ussuriensis which belongs to Euphorbiaceae has been used as a component of Korean traditional remedy against hepatitis and jaundice. Aqueous methanolic extract of P. ussuriensis was tested for antiviral activity of hepatitis B virus (HBV) in HepG2 2.2.15 cells which were derived through transfection of cloned HBV DNA into HepG2 human hrpatoblastoma cells. P. ussuriensis extract decreased the levels of extracellular HBV virion DNA and inhibited HBV replication at concentrations ranging from 50 to 500$\mu$g/ml. Partitioning of water suspension of the extract revealed that the activity mainly resides in the EtOAc fraction. Consecutive purification of the EtOAc fraction by silica-gel column chromatography resulted in the two active anti-HBV fractions. Southern blot analysis shows that the action mechanisms or active site of the two fractions seems to be different in terms of their inhibition of HBV replication steps.

• Journal of Microbiology
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• 제42권3호
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• pp.239-242
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• 2004

This study examined the detection rate of the hepatitis B virus (HBV) and Mycobacterium tuberculosis (Mtb) in serum and saliva samples, respectively, from 120 dental patients who were unaware if they have or had either hepatitis or tuberculosis. The frequencies of HBsAg and anti-HBs were determined using an immunochromatic assay. Mtb positivity was determined by the PCR method. Of the 120 patients, 7 (5.8％) were HBV positive and 30 (25.0％) were Mtb positive. This highlights the fact that dental health care workers (DHCWs) can be exposed to the risk of infection from blood- or saliva-borne pathogens as a consequence of their work. Therefore, it is very important to prevent cross infection between patients and dental personnel. Accordingly, laboratory tests prior to surgical treatment are needed to determine the infectious state of dental patients in order to prevent the transmission of infectious diseases in dental clinics.

• 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.

• 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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• 제16권13호
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• pp.5285-5288
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• 2015

Background: Hepatitis B virus (HBV) infection has been reported to be associated with inferior prognosis in hepatocellular and pancreatic carcinoma cases, but has not been studied with respect to non small cell lung cancer (NSCLC). The purpose of this study was to investigate the prognostic significance of HBV infection in advanced NSCLC patients. Materials and Methods: A retrospective cohort of 445 advanced NSCLC patients was recruited at our hospital from January 1, 2003 until August 30, 2014. Serum HBV markers were tested by enzyme-linked immunosorbent assay. COX proportional hazards analysis was used to evaluate associations of HBV infection with overall survival (OS). Results: Of 445 patients who were qualified for the study, 68 patients were positive for HBsAg, also considered as HBV infection. Patients in HBsAg negative group were found to have better OS (12.6 months [12.2-12.9]) than those in HBsAg positive group (11.30 months [10.8-11.9]; p=0.001). Furthermore, COX multivariate analysis identified HBV infection as an independent prognostic factor for OS (HR 0.740 [0.560, 0.978], p=0.034). Conclusions: Our study found that HBsAg-positive status was an independent prognostic factor for OS in patients with advanced NSCLC. Future prospective studies are required to confirm our findings.

• Journal of Microbiology and Biotechnology
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• 제10권6호
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• pp.844-850
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• 2000

The specific binding and internalization of viral particles is an essential step for the successful infection of viral pathogens. In the case of the hepatitis B virus (HBV), virions bind to the host cell via the preS domain of the viral surface antigen and are subsequently internalized by endocytosis. HBV-preS specific receptors are primarily expressed on hepatocytes, however, viral DNA and proteins have also been detected in extrahepatic sites, suggsting that celluar recepators for HBV may also exist on extrahepatic cells. Recently, an EBV-transformed B-cell line was identified onto which the preS region binds in a receptor-ligand specific manner. In this study, this specific interaction was further characterized, and the binding region within the preS protein was locaized. Also the internalization after host cell attachment was visualized and analyzed by fluorescence-labeled HBV-preS1 proteins using confocal microscopy. Energy depletion by sodium azide treatment effectively inhibited the internalization of the membrane-bound preS1 ligands, thereby indicating an energy-dependent receptor-mediated endocytotic pathway. Accordingly, the interaction of HBV-pres! with this specific B-cell line may serve as an effective model for an infection pathway in extrahepatic cells.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1994년도 춘계학술대회 and 제3회 신약개발 연구발표회
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• pp.178-178
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• 1994

Hepatitis B Virus (HBV) is a DNA virus with a 3.2kb partially double-stranded genome. The life cycle of the virus involves a reverse transcription of the greater than genome length 3.5kb mRNA. This pegenomic RNA contains all the genetic information encoded by the virus and functions as an intermediate in viral replication. Tumor suppressor p53 has previously been shown to interact with the X-gene product of the HBV, which led us to hypothesize that p53 may act as a negative regulator of HBV replication and the role of the X-gene product is to overcome the p53-mediated restriction. As a first step to prove the above hypothesis, we tested whether p53 represses the propagation of HBV in in vitro replication system. By transient cotransfection of the plasmid containing a complete copy of the HBV genome and/or the plasmid encoding p53, we found that the replication of HBV is specifically blocked by wild-type p53. The levels of HBV DNA, HBs Ag and HBc/e Ag secreted in cell culture media were dramatically reduced upon coexpresion of wild-type p53 but not by the coexpression of the mutants of p53 (G154V and R273L). Furthermore, levels of RNAs originated from HBV genome were repressed more than 10 fold by the cotransfection of the p53 encoding plasmid. These results clearly states that p53 is a nesative regulator of the HBV replication. Next, to addresss the mechanism by which p53 represses the HBV replication, we performed the transient transfection experiments employing the pregenomic/core promoter-CAT(Chloramphenicol Acetyl Transferase) construct as a reporter. Cotransfection of wild-type p53 but not the mutant p53 expression plasmids repressed the CAT activity more than 8 fold. Integrating the above results, we propose that p53 represses the replication of HBV specifically by the down-regulation of the pregenomic/core promoter, which results in the reduced DNA synthesis of HBV. Currently, the mechanism by which HBV overcomes the observed p53-mediated restriction of replication is tinder investigation.