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integrated HBV DNA

Noele P Nelson, Philippa J Easterbrook, Brian J McMahon
Integration of hepatitis B vaccination into national immunization programs has resulted in substantial reductions of hepatitis B virus (HBV) transmission in previously high endemic countries. The key strategy for control of the HBV epidemic is birth dose and infant vaccination. Additional measures include use of hepatitis B immunoglobulin (HBIG) and diagnosis of mothers at high risk of transmitting HBV and use of antiviral agents during pregnancy to decrease maternal DNA concentrations to undetectable concentrations...
November 2016: Clinics in Liver Disease
Baosheng Li, Shuo Sun, Minran Li, Xin Cheng, Haijun Li, Fubiao Kang, Jiwen Kang, Katharina Dörnbrack, Michael Nassal, Dianxing Sun
Chronic infection with hepatitis B virus (HBV), a small DNA virus that replicates by reverse transcription of a pregenomic (pg) RNA precursor, greatly increases the risk for terminal liver disease. RNA interference (RNAi) based therapy approaches have shown potential to overcome the limited efficacy of current treatments. However, synthetic siRNAs as well as small hairpin (sh) RNAs expressed from non-integrating vectors require repeated applications; integrating vectors suffer from safety concerns. We pursue a new concept by which HBV itself is engineered into a conditionally replicating, wild-type HBV dependent anti-HBV shRNA vector...
October 2016: Antiviral Research
Markus Cornberg, Vincent Wai-Sun Wong, Stephen Locarnini, Maurizia Brunetto, Harry L A Janssen, Henry Lik-Yuen Chan
In the past 10 years, there are a lot of enthusiasms on the use of serum hepatitis B surface antigen (HBsAg) quantification to predict disease activity and monitor treatment response in chronic hepatitis B. The measurement of HBsAg level has been standardized in IU/mL and nowadays it is almost mandatory with the development of new antiviral treatments as HBsAg seroclearance, i.e. functional cure of hepatitis B, is now considered the goal of therapy. Recently, improved understanding on molecular virology of HBsAg, particularly on the relative roles of covalently closed circular DNA and integrated HBV DNA, has shed new lights on the interpretation of HBsAg level in different phases of chronic hepatitis B...
August 26, 2016: Journal of Hepatology
C R Seed, P Kiely, V C Hoad, A J Keller
BACKGROUND AND OBJECTIVES: We previously published a model to estimate the residual risk (RR) for occult hepatitis B infection (OBI) in the absence of universal anti-HBc testing. To incorporate new information on the epidemiology of OBI, we describe model refinements and estimate a more accurate HBV RR due to OBI in Australia. MATERIALS AND METHODS: In our original model, the OBI risk, p(OBI), was defined by the rate of 'non-detection' by the HBV DNA screening test in use, p(NAT non-detection), and the average infectivity of blood components from OBI donors, p(transmission)...
August 26, 2016: Vox Sanguinis
William S Mason, Upkar S Gill, Samuel Litwin, Yan Zhou, Suraj Peri, Oltin Pop, Michelle L W Hong, Sandhia Naik, Alberto Quaglia, Antonio Bertoletti, Patrick T F Kennedy
BACKGROUND & AIMS: Chronic infection with hepatitis B virus (HBV) progresses through different phases. The first, called the immune-tolerant phase, has been associated with a lack of disease activity. We examined HBV-DNA integration, clonal hepatocyte expansion, HBV antigen expression, and HBV-specific immune responses in patients in the immune-tolerant phase to assess whether this designation is appropriate or if there is evidence of disease activity. METHODS: We studied HBV-DNA integration, clonal hepatocyte expansion, and expression of hepatitis B surface antigen and core antigen in liver tissues from 26 patients with chronic HBV infection (ages, 14-39 y); 9 patients were positive for hepatitis B e antigen (HBeAg) in the immune-tolerant phase and were matched for age with 10 HBeAg-positive patients with active disease and 7 HBeAg-negative patients with active disease...
July 22, 2016: Gastroenterology
Ma Li, Chen Hongyan, Zhu Huaxing, Li Wei, Lu Daru
Hepatitis B virus (HBV) is a dented double-stranded DNA virus. After infecting human hepatic cells, it forms cccDNA that replicates persistently and integrates randomly into the host’s genome during the process of reserve transcription. On average, in each cell with chronic HBV infection, there are about 33 copies of cccDNA with a half of 35-57 days, which can be difficult to eradicate. A new strategy is to inhibit HBV transcription by using locked nucleic acid (LNA). Besides, cleaving HBV genome by targeted genome editing technologies could potentially cure patients...
April 2016: Yi Chuan, Hereditas
Yong Wu, Tian-Ying Zhang, Lin-Lin Fang, Zi-Xuan Chen, Liu-Wei Song, Jia-Li Cao, Lin Yang, Quan Yuan, Ning-Shao Xia
The stable HBV-replicating cell lines, which carry replication-competent HBV genome stably integrated into the genome of host cell, are widely used to evaluate the effects of antiviral agents. However, current methods to generate HBV-replicating cell lines, which are mostly dependent on random integration of foreign DNA via plasmid transfection, are less-efficient and time-consuming. To address this issue, we constructed an all-in-one Sleeping Beauty transposon system (denoted pTSMP-HBV vector) for robust generation of stable cell lines carrying replication-competent HBV genome of different genotype...
August 2016: Journal of Virological Methods
Massimo Levrero, Jessica Zucman-Rossi
Hepatitis B virus (HBV) contributes to hepatocellular carcinoma (HCC) development through direct and indirect mechanisms. HBV DNA integration into the host genome occurs at early steps of clonal tumor expansion and induces both genomic instability and direct insertional mutagenesis of diverse cancer-related genes. Prolonged expression of the viral regulatory protein HBx and/or altered versions of the preS/S envelope proteins dysregulates cell transcription and proliferation control and sensitizes liver cells to carcinogenic factors...
April 2016: Journal of Hepatology
T A Semenenko, A P Suslov
The concept of occult infection caused by hepatitis B virus (HBV) is determined as the presence of HBV DNA in blood sera or liver with the absence of detectable HBsAg. The actuality of this problem is associated with the fact, that occult hepatitis B (OHB) can be transmitted during hemotransfusions, cause reactivation of chronic hepatitis B in immune compromised individuals, facilitate development of liver cirrhosis and hepatocellular carcinoma. Several different hypotheses of OHB immunopathogenesis have been proposed, including a low number of copies of HBV DNA, altered immune response of the macroorganism, genetic variability of the S gene, integration of viral DNA into host genome, infection of mononuclear cells of peripheral blood, presence of immune complexes that hide HBsAg, and interference by other viruses such as HCV and HIV...
November 2015: Zhurnal Mikrobiologii, Epidemiologii, i Immunobiologii
Caecilia H C Sukowati, Korri E El-Khobar, Susan I Ie, Beatrice Anfuso, David H Muljono, Claudio Tiribelli
Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide. Chronic infection of hepatitis B virus (HBV) and/or hepatitis C virus (HCV) is a major risk factor in the development of the HCC, independently from excessive alcohol abuse and metabolic disease. Since the biology of HBV and HCV is different, their oncogenic effect may go through different mechanisms, direct and/or indirect. Viral hepatitis infection is associated with cellular inflammation, oxidative stress, and DNA damage, that may lead to subsequent hepatic injuries such as chronic hepatitis, fibrosis, cirrhosis, and finally HCC...
January 28, 2016: World Journal of Gastroenterology: WJG
Daisy P F Tsang, William K K Wu, Wei Kang, Ying-Ying Lee, Feng Wu, Zhuo Yu, Lei Xiong, Anthony W Chan, Joanna H Tong, Weiqin Yang, May S M Li, Suki S Lau, Xiangchun Li, Sau-Dan Lee, Yihua Yang, Paul B S Lai, Dae-Yeul Yu, Gang Xu, Kwok-Wai Lo, Matthew T V Chan, Huating Wang, Tin L Lee, Jun Yu, Nathalie Wong, Kevin Y Yip, Ka-Fai To, Alfred S L Cheng
Enhancer of zeste homolog 2 (EZH2) catalyses histone H3 lysine 27 trimethylation (H3K27me3) to silence tumour-suppressor genes in hepatocellular carcinoma (HCC) but the process of locus-specific recruitment remains elusive. Here we investigated the transcription factors involved and the molecular consequences in HCC development. The genome-wide distribution of H3K27me3 was determined by chromatin immunoprecipitation coupled with high-throughput sequencing or promoter array analyses in HCC cells from hepatitis B virus (HBV) X protein transgenic mouse and human cell models...
April 2016: Journal of Pathology
Lemonica Koumbi, Peter Karayiannis
Epigenetic modifications are stable alterations in gene expression that do not involve mutations of the genetic sequence itself. It has become increasingly clear that epigenetic factors contribute to the outcome of chronic hepatitis B virus (HBV) infection by affecting cellular and virion gene expression, viral replication and the development of hepatocellular carcinoma. HBV persists in the nucleus of infected hepatocytes as a stable non-integrated covalently closed circular DNA (cccDNA) which functions as a minichromosome...
2015: Frontiers in Microbiology
Yanan Pang, Weixing Guo, Jiaqi Wang, Guixia Xu, Kai Cheng, Guangwen Cao, Mengchao Wu, Shuqun Cheng, Shanrong Liu
Integration of hepatitis B virus (HBV) DNA into the human liver cell genome is believed to promote HBV-related carcinogenesis. This study aimed to quantify the integration of HBV DNA into the leukocyte genome in hepatocellular carcinoma (HCC) patients in order to identify potential biomarkers for HBV-related diseases. Whole-genome comparative genomic hybridization (CGH) chip array analyses were performed to screen gene copy number variations (CNV) in the leukocyte genome, and the results were confirmed by quantitative polymerase chain reaction (qPCR)...
February 16, 2016: Oncotarget
Berthold Bivigou-Mboumba, Sandrine François-Souquière, Luc Deleplancque, Jeanne Sica, Augustin Mouinga-Ondémé, Marie Amougou-Atsama, Marie-Laure Chaix, Richard Njouom, François Rouet
Integrated data on hepatitis B virus (HBV) patterns, HBV genotypes and mutations are lacking in human immunodeficiency virus type 1 (HIV-1) co-infected patients from Africa. This survey was conducted in 2010-2013 among 762 HIV-1-positive adults from Gabon who were predominantly treated with 3TC-based antiretroviral treatment. HBV patterns were identified using immunoassays detecting total antibody to hepatitis B core antigen (HBcAb), hepatitis B surface antigen (HBsAg), IgM HBcAb, hepatitis B e antigen (HBeAg), antibody to HBsAg (HBsAb) and an in-house real-time PCR test for HBV DNA quantification...
2016: PloS One
Margaret Littlejohn, Stephen Locarnini, Lilly Yuen
Members of the family Hepadnaviridae fall into two subgroups: mammalian and avian. The detection of endogenous avian hepadnavirus DNA integrated into the genomes of zebra finches has revealed a deep evolutionary origin of hepadnaviruses that was not previously recognized, dating back at least 40 million and possibly >80 million years ago. The nonprimate mammalian members of the Hepadnaviridae include the woodchuck hepatitis virus (WHV), the ground squirrel hepatitis virus, and arctic squirrel hepatitis virus, as well as a number of members of the recently described bat hepatitis virus...
January 2016: Cold Spring Harbor Perspectives in Medicine
Franziska Graumann, Yuri Churin, Annette Tschuschner, Kurt Reifenberg, Dieter Glebe, Martin Roderfeld, Elke Roeb
OBJECTIVE: The Hepatitis B virus genome persists in the nucleus of virus infected hepatocytes where it serves as template for viral mRNA synthesis. Epigenetic modifications, including methylation of the CpG islands contribute to the regulation of viral gene expression. The present study investigates the effects of spontaneous age dependent loss of hepatitis B surface protein- (HBs) expression due to HBV-genome specific methylation as well as its proximate positive effects in HBs transgenic mice...
2015: PloS One
Mohammad Hossein Mashhadizadeh, Rasoul Pourtaghavi Talemi
A magnetite and gold nanoparticle modified carbon paste electrode (CPE) was prepared for the immobilization of a thiol modified Hepatitis B virus (HBV) probe DNA and determination trace amount of target HBV DNA. Indeed, the sensing platform integrated two nanoparticles that had previously been employed individually in the DNA biosensors. The proposed DNA biosensor could measure target HBV DNA virus concentration with a low detection limit of 3.1 (±0.1)×10-(13)M, which was greatly lower than the detection limit reported with gold or magnetite nanoparticles alone...
February 2016: Materials Science & Engineering. C, Materials for Biological Applications
Simon B Larsson, Sebastian Malmström, Charles Hannoun, Gunnar Norkrans, Magnus Lindh
BACKGROUND: Hepatitis B virus (HBV) DNA in serum of chronically infected patients declines by 3-4 log10 units at loss of HBe antigen (HBeAg) from serum. The mechanisms behind this decline, and the much smaller decline of surface antigen (HBsAg) levels, are still not well known. The aim of this study was to get a better understanding of this process by analysing both serum and intrahepatic markers of HBV replication. METHODS: Levels of HBV DNA and HBsAg in serum, and covalently closed circular DNA (cccDNA), pregenomic RNA (pgRNA) and S-RNA and total intrahepatic HBV DNA (ihDNA) in liver biopsies from 84 chronically infected patients (16 positive and 68 negative for HBeAg) were analysed...
December 9, 2015: Virology Journal
Patricia M Mulrooney-Cousins, Tomasz I Michalak
Woodchuck hepatitis virus (WHV) is molecularly and pathogenically closely related to hepatitis B virus (HBV). Both viruses display tropism towards hepatocytes and cells of the immune system and cause similar liver pathology, where acute hepatitis can progress to chronic hepatitis and to hepatocellular carcinoma (HCC). Two forms of occult hepadnaviral persistence were identified in the woodchuck-WHV model: secondary occult infection (SOI) and primary occult infection (POI). SOI occurs after resolution of a serologically apparent infection with hepatitis or after subclinical serologically evident virus exposure...
September 28, 2015: Journal of Clinical and Translational Hepatology
Janet M Doolittle-Hall, Danielle L Cunningham Glasspoole, William T Seaman, Jennifer Webster-Cyriaque
Oncoviruses cause tremendous global cancer burden. For several DNA tumor viruses, human genome integration is consistently associated with cancer development. However, genomic features associated with tumor viral integration are poorly understood. We sought to define genomic determinants for 1897 loci prone to hosting human papillomavirus (HPV), hepatitis B virus (HBV) or Merkel cell polyomavirus (MCPyV). These were compared to HIV, whose enzyme-mediated integration is well understood. A comprehensive catalog of integration sites was constructed from the literature and experimentally-determined HPV integration sites...
November 10, 2015: Cancers
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