The M539V Polymerase Variant of Human Hepatitis B Virus Demonstrates Resistance to 2′-Deoxy-3′-Thiacytidine and a Reduced Ability to Synthesize Viral DNA

1998 ◽  
Vol 42 (8) ◽  
pp. 2128-2131 ◽  
Author(s):  
Stephanie K. Ladner ◽  
Thomas J. Miller ◽  
Robert W. King
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hbv Infection ◽  
Wild Type ◽  
Viral Dna ◽  
Transfected Cells ◽  
Transplant Patients ◽  
Antiviral Effects ◽  
Chronic Hepatitis B Virus ◽  
B Virus

ABSTRACT The cytosine analog 2′-deoxy-3′-thiacytidine (3TC) has been shown to be an effective treatment for chronic hepatitis B virus (HBV) infection. However, several liver transplant patients who were undergoing treatment with 3TC for HBV infection experienced a breakthrough of virus while on 3TC. The predominant virus found in these patients’ sera contained either a valine or isoleucine for the methionine in the highly conserved YMDD nucleotide binding site in the HBV polymerase. To determine the biological relevance of the Met-to-Val substitution, we mutated a plasmid that contained a cDNA copy of the HBV pregenomic RNA such that when virus replication occurred during transient transfection of HepG2 cells, an M539V polymerase variant was produced. We found that in transiently transfected cells, this variant was approximately 330-fold less sensitive to the antiviral effects of 3TC and produced 7-fold less viral DNA than the wild type.

High prevalence of occult hepatitis C virus infection in patients with chronic hepatitis B virus infection

2013 ◽  
Vol 62 (8) ◽  
pp. 1235-1238 ◽  
Author(s):  
Inmaculada Castillo ◽  
Javier Bartolomé ◽  
Juan Antonio Quiroga ◽  
Vicente Carreño
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Hepatitis B Virus ◽  
Virus Infection ◽  
Hepatitis B ◽  
Hcv Infection ◽  
Hbv Infection ◽  
Chronic Hepatitis B Virus ◽  
B Virus

Hepatitis C virus (HCV) infection in the absence of detectable antibodies against HCV and of viral RNA in serum is called occult HCV infection. Its prevalence and clinical significance in chronic hepatitis B virus (HBV) infection is unknown. HCV RNA was tested for in the liver samples of 52 patients with chronic HBV infection and 21 (40 %) of them were positive for viral RNA (occult HCV infection). Liver fibrosis was found more frequently and the fibrosis score was significantly higher in patients with occult HCV than in negative ones, suggesting that occult HCV infection may have an impact on the clinical course of HBV infection.

scholarly journals Creation of a Six-fingered Artificial Transcription Factor That Represses the Hepatitis B Virus HBx Gene Integrated into a Human Hepatocellular Carcinoma Cell Line

2012 ◽  
Vol 18 (4) ◽  
pp. 378-387 ◽  
Author(s):  
Xinghui Zhao ◽  
Zhanzhong Zhao ◽  
Junwei Guo ◽  
Peitang Huang ◽  
Xudong Zhu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Transcription Factor ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Cell Line ◽  
Hbv Infection ◽  
Luciferase Reporter ◽  
Artificial Transcription Factor ◽  
Chronic Hepatitis B Virus ◽  
B Virus

Chronic hepatitis B virus (HBV) infection is an independent risk factor for the development of hepatocellular carcinoma (HCC). The HBV HBx gene is frequently identified as an integrant in the chromosomal DNA of patients with HCC. HBx encodes the X protein (HBx), a putative viral oncoprotein that affects transcriptional regulation of several cellular genes. Therefore, HBx may be an ideal target to impede the progression of HBV infection–related HCC. In this study, integrated HBx was transcriptionally downregulated using an artificial transcription factor (ATF). Two three-fingered Cys2-His2 zinc finger (ZF) motifs that specifically recognized two 9-bp DNA sequences regulating HBx expression were identified from a phage-display library. The ZF domains were linked into a six-fingered protein that specified an 18-bp DNA target in the Enhancer I region upstream of HBx. This DNA-binding domain was fused with a Krüppel-associated box (KRAB) transcriptional repression domain to produce an ATF designed to downregulate HBx integrated into the Hep3B HCC cell line. The ATF significantly repressed HBx in a luciferase reporter assay. Stably expressing the ATF in Hep3B cells resulted in significant growth arrest, whereas stably expressing the ATF in an HCC cell line lacking integrated HBx (HepG2) had virtually no effect. The targeted downregulation of integrated HBx is a promising novel approach to inhibiting the progression of HBV infection–related HCC.

Discovery of novel hepatitis B virus (HBV) antivirals and analysis of mechanisms of action of HBV-targeting agents

2017 ◽  
Author(s):  
◽  
Andrew Douglas Huber
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Treatment Options ◽  
Mechanisms Of Action ◽  
Hbv Infection ◽  
Viral Inhibition ◽  
University Of Missouri ◽  
Chronic Hepatitis B Virus ◽  
B Virus

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Chronic hepatitis B virus (HBV) infection leads to liver disease, cirrhosis, and hepatocellular carcinoma. Globally, an estimated 50% of all hepatocellular carcinoma cases are linked to chronic HBV infection. More than 240 million people are chronically infected, and there are 0.5-1 million deaths per year due to HBVrelated liver conditions. HBV treatment options rarely cure infections and are associated with adverse side effects that often outweigh the potential benefits of treatment. New treatments, therefore, are highly desired for HBV therapy. Towards this goal, we have developed novel compounds targeting two viral targets and assessed the mechanisms of action by which these compounds act. We have developed systems for the discovery and evaluation of compounds that inhibit 2 distinct steps in the HBV life cycle. Using these systems, we have developed potent inhibitors of HBV replication that have potential to become clinically used HBV drugs. Furthermore, we have used our methods to evaluate which properties of these compounds are likely to result in better viral inhibition. The work described in this thesis has led to at least 2 new compound groups for potential use as HBV antivirals and provides insight into mechanisms by which potent antivirals can be achieved.

scholarly journals Analysis of the complete genome of hepatitis B virus subgenotype C2 isolate NHB17965 from a HBV infected patient

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1023 ◽  
Author(s):  
Modhusudon Shaha ◽  
Palash Kumar Sarker ◽  
Md. Saddam Hossain ◽  
Keshob Chandra Das ◽  
Munira Jahan ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Complete Genome ◽  
Infected Patient ◽  
Surface Proteins ◽  
Wild Type ◽  
Small Surface ◽  
Chronic Hepatitis B Virus ◽  
B Virus ◽  
Complete Genome Analysis

The burden of chronic hepatitis B virus (HBV) infections is increasingly detected nowadays. Herein, we report a complete genome of HBV subgenotype C2 (HBV/C2) from a HBV infected patient. Complete genome analysis revealed that the isolated strain was a non-recombinant wild type and had several regular substitutions in the reverse transcriptase domain and small surface proteins of HBV. This study may help clinicians and scientists gain in-depth knowledge on the current substitutions of HBV/C2 genome and to identify potential therapies against HBV infections.

scholarly journals Hepatitis B Virus Replication Induces Methylation of both Host and Viral DNA

2010 ◽  
Vol 84 (9) ◽  
pp. 4321-4329 ◽  
Author(s):  
Perumal Vivekanandan ◽  
Hubert Darius-J Daniel ◽  
Rajesh Kannangai ◽  
Francisco Martinez-Murillo ◽  
Michael Torbenson
Keyword(s):  
Gene Expression ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Viral Replication ◽  
Cell Lines ◽  
Natural Infection ◽  
Cpg Islands ◽  
Hbv Infection ◽  
Viral Dna ◽  
B Virus

ABSTRACT Control of viral replication is a major therapeutic goal to reduce morbidity and mortality from chronic hepatitis B virus (HBV) infection. Recently, methylation has been identified as a novel host defense mechanism, and methylation of viral DNA leads to downregulation of HBV gene expression. To better understand the mechanisms of HBV methylation, cell lines were exposed to HBV using a model system that mimics natural infection and the expression of host DNA methyltransferase genes (DNMTs) was measured. DNMT1, DNMT2, and DNMT3 were all significantly upregulated in response to HBV. DNMT3 was further studied because of its known role in the de novo methylation of DNA. Cotransfection experiments with full-length HBV and DNMT3 led to the downregulation of viral protein and pregenomic RNA production. To investigate whether the upregulation of DNMTs could also have an effect on the methylation of host DNA, cell lines were exposed to HBV in two independent model systems, one that mimics natural infection and a second model with temporary transfection. Host DNA methylation was measured by DNA microarray analysis. Increased methylation of host CpG islands was detected in both experimental systems. Two CpG islands, corresponding to genes SUFU and TIRAP, were selected, and the downregulation of these genes in hepatocellular carcinomas was confirmed. In conclusion, hepatocytes respond to HBV infection by upregulating DNMTs. The DNMTs methylate viral DNA, leading to decreased viral gene expression and decreased viral replication. However, virus-induced overexpression of DNMTs also leads to methylation of host CpG islands.

Pregnancy Complicated With Hepatitis B Virus Infection and Preterm Birth: A Retrospective Cohort Study

2021 ◽  
Author(s):  
Shuisen Zheng ◽  
Huale Zhang ◽  
Rongxin Chen ◽  
Jianying Yan ◽  
Qing Han
Keyword(s):  
Risk Factor ◽  
Preterm Birth ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Pregnant Women ◽  
Hbv Infection ◽  
Confounding Factors ◽  
Logistics Regression ◽  
Chronic Hepatitis B Virus ◽  
B Virus

Abstract Background: We aimed to investigate whether maternal chronic hepatitis B virus (HBV) infection affects preterm birth（PTB) in pregnant women. Methods: We retrospectively analyzed HBV-infected and non-infected pregnant women attending antenatal care at Fujian Provincial Maternity and Child Health Hospital, Fuzhou, China between January 1, 2016 to December 31, 2018. Participants were divided into HBV infection (n = 1302) and control (n = 12813) groups. We compared baseline data, pregnancy and perinatal complications, and preterm delivery outcomes between groups and performed subgroup comparisons and multiple logistics regression analysis to adjust for confounding factors. Results: The incidence of PTBs before 37 weeks was similar between the groups. PTBs before 34 weeks were significantly more among the HBV infection group than among the controls (1.6% VS. 0.8% ; P = 0.003) After adjusting for confounding factors through logistics regression, HBV infection was found to be an independent PTB risk factor before 34 weeks gestation (adjusted odds ratio 1.796; 95% confidence interval[1.071, 3.012]). According to the subgroup analysis based on whether hepatitis B e-antigen (HBeAg) was positive and whether alanine aminotransferase (ALT) levels were normal during the second trimester, PTB was more frequent in HBeAg negative HBV infection before 34 weeks than among controls(1.8% VS. 0.8%). The PTB rate for pregnant women with normal ALT and HBV infection before 34 weeks was higher than that of the controls (1.6% VS. 0.8%) Conclusion HBV infection is an independent risk factor for PTB before 34 weeks. Comprehensive programs focusing on pregnant women with HBV infection would reduce the incidence of adverse outcomes.

The Clinical Presentation of Chronic Hepatitis B Virus (HBV) Infection in Asian Americans

2009 ◽  
pp. 1
Author(s):  
Jonathan S. Mellen ◽  
Victor W. Xia ◽  
Mehrtash Hashemzadeh ◽  
David Imagawa ◽  
Mazen Jamal ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Asian Americans ◽  
Clinical Presentation ◽  
Hbv Infection ◽  
Chronic Hepatitis B Virus ◽  
B Virus
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