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https://www.readbyqxmd.com/read/29765512/dhx9-regulates-production-of-hepatitis-b-virus-derived-circular-rna-and-viral-protein-levels
#1
Kazuma Sekiba, Motoyuki Otsuka, Motoko Ohno, Takahiro Kishikawa, Mari Yamagami, Tatsunori Suzuki, Rei Ishibashi, Takahiro Seimiya, Eri Tanaka, Kazuhiko Koike
Hepatitis B virus (HBV) infection, which is a major health concern worldwide, can lead to liver cirrhosis and hepatocellular carcinoma. Although current nucleos(t)ide analogs efficiently inhibit viral reverse transcription and viral DNA load clinically, episomal viral covalently closed circular DNA (cccDNA) minichromosomes and transcripts from cccDNA continue to be expressed over the long term. We hypothesized that, under these conditions, viral transcripts may have biological functions involved in pathogenesis...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29734472/hbv-serum-dna-and-rna-levels-in-nucleos-t-ide-analogue-treated-or-untreated-patients-during-chronic-and-acute-infection
#2
Emily K Butler, Jeffrey Gersch, Anne McNamara, Ka-Cheung Luk, Vera Holzmayer, Maria de Medina, Eugene Schiff, Mary Kuhns, Gavin A Cloherty
Treatment of chronic hepatitis B (CHB) patients with nucleos(t)ide analogues (NA) suppresses HBV DNA synthesis but does not affect synthesis of HBV pregenomic RNA (pgRNA). HBV pgRNA is detectable in the serum during NA treatment and has been proposed as a marker of HBV covalently closed circular DNA (cccDNA) activity within the infected hepatocyte. We developed an automated assay for the quantification of serum HBV pgRNA using a dual-target qRT-PCR approach on the Abbott m2000sp/rt system. We demonstrate accurate detection and quantification of serum HBV RNA...
May 7, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29679386/hepatitis-b-virus-evasion-from-cgas-sensing-in-human-hepatocytes
#3
Eloi R Verrier, Seung-Ae Yim, Laura Heydmann, Houssein El Saghire, Charlotte Bach, Vincent Turon-Lagot, Laurent Mailly, Sarah C Durand, Julie Lucifora, David Durantel, Patrick Pessaux, Nicolas Manel, Ivan Hirsch, Mirjam B Zeisel, Nathalie Pochet, Catherine Schuster, Thomas F Baumert
Chronic hepatitis B virus (HBV) infection is a major cause of chronic liver disease and cancer worldwide. The mechanisms of viral genome sensing and the evasion of innate immune responses by HBV infection are still poorly understood. Recently, the cyclic GMP-AMP synthase (cGAS) was identified as a DNA sensor. In this study, we aimed to investigate the functional role of cGAS in sensing of HBV infection and elucidate the mechanisms of viral evasion. We performed functional studies including loss- and gain-of-function experiments combined with cGAS effector gene expression profiling in an infectious cell culture model, primary human hepatocytes and HBV-infected human liver chimeric mice...
April 20, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29677098/update-treatment-for-hbv-infection-and-persistent-risk-for-hepatocellular-carcinoma-prospect-for-an-hbv-cure
#4
REVIEW
Joseph Yoo, Hie-Won Hann, Robert Coben, Mitchell Conn, Anthony J DiMarino
Since the discovery of the hepatitis B virus (HBV) by Blumberg et al. in 1965, its genome, sequence, epidemiology, and hepatocarcinogenesis have been elucidated. Globally, hepatitis B virus (HBV) is still responsible for the majority of hepatocellular carcinoma (HCC). HCC is the sixth-most common cancer in the world and the second-most common cancer death. The ultimate goal of treating HBV infection is the prevention of HCC. Fortunately, anti-HBV treatment with nucleos(t)ide analogues (NAs), which began with lamivudine in 1998, has resulted in remarkable improvements in the survival of patients with chronic hepatitis B and a reduced incidence of HCC...
April 20, 2018: Diseases (Basel)
https://www.readbyqxmd.com/read/29656833/a-highly-sensitive-and-robust-method-for-hepatitis-b-virus-covalently-closed-circular-dna-detection-in-single-cells-and-serum
#5
Jing-Tao Huang, Ying Yang, Yi-Min Hu, Xing-Hui Liu, Mei-Yan Liao, Roy Morgan, Er-Feng Yuan, Xia Li, Song-Mei Liu
Despite implications of persistence of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) in the development of hepatocellular carcinoma (HCC), little is known about serum cccDNA in HBV-infected diseases. We developed a cccDNA-selective droplet digital PCR (ddPCR) to assess cccDNA content and dynamics across different stages of HCC development. One hundred forty-seven serum samples and 35 formalin-fixed, paraffin-embedded tumor tissues were derived from patients with HCC or HBV hepatitis/cirrhosis...
May 2018: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/29649127/gene-therapy-for-chronic-hbv-can-we-eliminate-cccdna
#6
REVIEW
Kristie Bloom, Mohube Betty Maepa, Abdullah Ely, Patrick Arbuthnot
Chronic infection with the hepatitis B virus (HBV) is a global health concern and accounts for approximately 1 million deaths annually. Amongst other limitations of current anti-HBV treatment, failure to eliminate the viral covalently closed circular DNA (cccDNA) and emergence of resistance remain the most worrisome. Viral rebound from latent episomal cccDNA reservoirs occurs following cessation of therapy, patient non-compliance, or the development of escape mutants. Simultaneous viral co-infections, such as by HIV-1, further complicate therapeutic interventions...
April 12, 2018: Genes
https://www.readbyqxmd.com/read/29627260/design-synthesis-and-biological-evaluation-of-seco-a-pentacyclic-triterpenoids-3-4-lactone-as-potent-non-nucleoside-hbv-inhibitors
#7
Zhijian Li, Qingxi Min, Haoji Huang, Ruixuan Liu, Yongyan Zhu, Quanhong Zhu
A series of seco-A-pentacyclic triterpenoids-3,4-lactone were synthesized and the anti-HBV activities were evaluated in vitro. Several compounds inhibited the secretion of HBV antigen and the replication of HBV DNA in micromolar level. Compounds D7 and D10, seco-A-oleanane-3,4-lactone, suppressed the HBeAg secretion with IC50 values of 0.14 μM and 0.86 μM respectively, and the inhibitory activities were also confirmed by detecting the fluorescence intensity of FITC-labeled monoclonal mouse HBeAg antibody via flow cytometry...
March 29, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29624717/sirt3-restricts-hbv-transcription-and-replication-via-epigenetic-regulation-of-cccdna-involving-suv39h1-and-setd1a-histone-methyltransferases
#8
Ji-Hua Ren, Jie-Li Hu, Sheng-Tao Cheng, Hai-Bo Yu, Vincent Kam Wai Wong, Betty Yuen Kwan Law, Yong-Feng Yang, Ying Huang, Yi Liu, Wei-Xian Chen, Xue-Fei Cai, Hua Tang, Yuan Hu, Wen-Lu Zhang, Xiang Liu, Quan-Xin Long, Li Zhou, Na-Na Tao, Hong-Zhong Zhou, Qiu-Xia Yang, Fang Ren, Lin He, Rui Gong, Ai-Long Huang, Juan Chen
Hepatitis B virus (HBV) infection remains a major health problem worldwide. Maintenance of the covalently closed circular DNA (cccDNA) which serves as a template for HBV RNA transcription is responsible for the failure of eradicating chronic HBV during current antiviral therapy. cccDNA is assembled with cellular histone proteins into chromatin, but little is known about the regulation of HBV chromatin by histone posttranslational modifications. In this study, we identified SIRT3 as a host factor restricting HBV transcription and replication by screening seven members of Sirtuin family which is the class III histone deacetylase...
April 6, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29621551/quantitation-of-hbv-cccdna-in-anti-hbc-positive-liver-donors-by-droplet-digital-pcr-a-new-tool-to-detect-occult-infection
#9
Gian Paolo Caviglia, Maria Lorena Abate, Francesco Tandoi, Alessia Ciancio, Antonio Amoroso, Mauro Salizzoni, Giorgio Maria Saracco, Mario Rizzetto, Renato Romagnoli, Antonina Smedile
BACKGROUND & AIMS: The accurate diagnosis of occult HBV infection (OBI) requires the demonstration of HBV DNA in liver biopsies of HBsAg-negative subjects. However, in clinical practice a latent OBI is deduced by the finding of the antibody to the HB-core antigen (anti-HBc). We investigated the true prevalence of OBI and the molecular features of intrahepatic HBV in anti-HBc-positive subjects. METHODS: The livers of 100 transplant donors (median age 68.2 years; 64 males, 36 females) positive for anti-HBc at standard serologic testing, were examined for total HBV DNA by nested-PCR and for the HBV covalently closed circular DNA (HBV cccDNA) with an in-house droplet digital PCR assay (ddPCR) (Linearity: R2 = 0...
April 2, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29599899/reactivation-of-hepatitis-b-after-liver-transplantation-current-knowledge-molecular-mechanisms-and-implications-in-management
#10
REVIEW
Ranjit Chauhan, Shilpa Lingala, Chiranjeevi Gadiparthi, Nivedita Lahiri, Smruti R Mohanty, Jian Wu, Tomasz I Michalak, Sanjaya K Satapathy
Chronic hepatitis B (CHB) is a major global health problem affecting an estimated 350 million people with more than 786000 individuals dying annually due to complications, such as cirrhosis, liver failure and hepatocellular carcinoma (HCC). Liver transplantation (LT) is considered gold standard for treatment of hepatitis B virus (HBV)-related liver failure and HCC. However, post-transplant viral reactivation can be detrimental to allograft function, leading to poor survival. Prophylaxis with high-dose hepatitis B immunoglobulin (HBIG) and anti-viral drugs have achieved remarkable progress in LT by suppressing viral replication and improving long-term survival...
March 27, 2018: World Journal of Hepatology
https://www.readbyqxmd.com/read/29599452/direct-antiviral-properties-of-tlr-ligands-against-hbv-replication-in-immune-competent-hepatocytes
#11
Julie Lucifora, Marc Bonnin, Ludovic Aillot, Floriane Fusil, Sarah Maadadi, Laura Dimier, Maud Michelet, Océane Floriot, Anaïs Ollivier, Michel Rivoire, Malika Ait-Goughoulte, Stéphane Daffis, Simon P Fletcher, Anna Salvetti, François-Loïc Cosset, Fabien Zoulim, David Durantel
Current therapies for chronic hepatitis B virus (HBV) infections are effective at decreasing the viral load in serum, but do not lead to viral eradication. Recent studies highlighted the therapeutic or "adjuvant" potential of immune-modulators. Our aim was to explore the direct anti-HBV effect of Toll-Like-Receptors (TLR) agonists in hepatocytes. HBV-infected primary human hepatocytes (PHH) or differentiated HepaRG cells (dHepaRG) were treated with various TLR agonists. Amongst all TLR ligands tested, Pam3CSK4 (TLR1/2-ligand) and poly(I:C)-(HMW) (TLR3/MDA5-ligand) were the best at reducing all HBV parameters...
March 29, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29596494/high-rates-of-chronic-hbv-genotype-e-infection-in-a-group-of-migrants-in-italy-from-west-africa-virological-characteristics-associated-with-poor-immune-clearance
#12
Vincenzo Malagnino, Romina Salpini, Gaetano Maffongelli, Arianna Battisti, Lavinia Fabeni, Lorenzo Piermatteo, Luna Colagrossi, Vanessa Fini, Alessandra Ricciardi, Cesare Sarrecchia, Carlo Federico Perno, Massimo Andreoni, Valentina Svicher, Loredana Sarmati
Hepatitis B virus (HBV) genotype E almost exclusively occurs in African people, and its presence is more commonly associated with the development of chronic HBV (CHB) infection. Moreover, an epidemiological link has been found between the distribution of HBV genotype E infection and African countries with high incidences of hepatocellular carcinoma. As part of a programme for the health assessment of migrants, we evaluated 358 young African subjects for HBV infection; 58.1% (208/358) were positive for an HBV marker, and 54 (25...
2018: PloS One
https://www.readbyqxmd.com/read/29580980/tumor-suppressor-zhx2-restricts-hepatitis-b-virus-replication-via-epigenetic-and-non-epigenetic-manners
#13
Leiqi Xu, Zhuanchang Wu, Siyu Tan, Zehua Wang, Qinghai Lin, Xiaoyan Li, Xiaojia Song, Yuan Liu, Yang Song, Jie Zhang, Jun Peng, Lifen Gao, Yaoqin Gong, Xiaohong Liang, Xiuli Zuo, Chunhong Ma
Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA), the stable genomic form as the template for viral transcription, plays a crucial role in viral persistence which remains a major global health problem. While accumulating evidence suggests the involvement of transcription factors and epigenetic machinery in cccDNA transcription, the roles of host transcription factors which contribute to epigenetic modification of cccDNA remain largely unknown. Zinc finger and homeoboxes 2 (ZHX2) is abundantly expressed in adult hepatocytes, where it acts as a transcriptional repressor and tumor suppressor by directly inhibiting the promoter activities of target genes...
May 2018: Antiviral Research
https://www.readbyqxmd.com/read/29572897/acute-hbv-infection-in-humanized-chimeric-mice-has-multiphasic-viral-kinetics
#14
Yuji Ishida, Tje Lin Chung, Michio Imamura, Nobuhiko Hiraga, Suranjana Sen, Hiroshi Yokomichi, Chise Tateno, Laetitia Canini, Alan S Perelson, Susan L Uprichard, Harel Dahari, Kazuaki Chayama
BACKGROUND: Chimeric uPA/SCID mice reconstituted with humanized livers are useful for studying HBV infection in the absence of an adaptive immune response. However, the detailed characterization of HBV infection kinetics necessary to enable in-depth mechanistic studies in this novel in vivo HBV infection model is lacking. METHODS: To characterize HBV kinetics post-inoculation (p.i.) to steady state, 42 mice were inoculated with HBV. Serum HBV DNA was frequently measured from 1 minute to 63 days p...
March 23, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29555628/preclinical-profile-of-ab-423-an-inhibitor-of-hepatitis-b-virus-pgrna-encapsidation
#15
Nagraj Mani, Andrew G Cole, Janet R Phelps, Andrzej Ardzinski, Kyle D Cobarrubias, Andrea Cuconati, Bruce D Dorsey, Ellen Evangelista, Kristi Fan, Fang Guo, Haitao Guo, Ju-Tao Guo, Troy O Harasym, Salam Kadhim, Steven G Kultgen, Amy C H Lee, Alice H L Li, Quanxin Long, Sara A Majeski, Richeng Mao, Kevin D McClintock, Stephen P Reid, Rene Rijnbrand, Nicholas M Snead, Holly M Micolochick Steuer, Kim Stever, Sunny Tang, Xiaohe Wang, Qiong Zhao, Michael J Sofia
AB-423 is a sulfamoylbenzamide (SBA) class of HBV capsid inhibitor in Phase 1 clinical trials. In cell culture models AB-423 showed potent inhibition of HBV replication (EC50 /EC90 = 0.08-0.27 μM/0.33-1.32 μM) with no significant cytotoxicity (CC50 >10 μM). Addition of 40% human serum resulted in a 5-fold increase in the EC50 values. AB-423 inhibited HBV genotypes A through D and nucleos/tide-resistant variants in vitro Treatment of HepDES19 cells with AB-423 resulted in capsid particles devoid of encapsidated pgRNA and rcDNA indicating it is a class II capsid inhibitor...
March 19, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29528436/divergent-pres-sequences-in-virion-associated-hepatitis-b-virus-genomes-and-subviral-hbv-surface-antigen-particles-from-hbv-e-antigen-negative-patients
#16
Kai-Henrik Peiffer, Lisa Kuhnhenn, Bingfu Jiang, Antonia Mondorf, Johannes Vermehren, Viola Knop, Simone Susser, Dirk Walter, Julia Dietz, Gert Carra, Fabian Finkelmeier, Stefan Zeuzem, Christoph Sarrazin, Eberhard Hildt
Background: The hepatitis B virus (HBV) surface proteins (HBsAg) coat the viral particle and form subviral particles (SVPs). Loss of HBsAg represents a functional cure and is an important treatment goal. Methods: We analyzed the impact of the HBV genotypes A-E and pre-S mutations on SVP expression in HBeAg negative chronic HBV infected patients. A HBV genome harboring a preS1-deletion was analyzed in hepatoma cells. Results: We observed a genotype-specific ratio of the three surface proteins (SHBs/MHBs/LHBs), which reflects differences in the morphology and composition of SVPs...
March 8, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29491161/relative-abundance-of-integrant-derived-viral-rnas-in-infected-tissues-harvested-from-chronic-hepatitis-b-virus-carriers
#17
Natalia Freitas, Tetyana Lukash, Sumedha Gunewardena, Benjamin Chappell, Betty L Slagle, Severin O Gudima
Five matching sets of nonmalignant liver tissues and hepatocellular carcinoma (HCC) samples from individuals chronically infected with hepatitis B virus (HBV) were examined. The HBV genomic sequences were determined by using overlapping PCR amplicons covering the entire viral genome. Four pairs of tissues were infected with HBV genotype C, while one pair was infected with HBV genotype B. HBV replication markers were found in all tissues. In the majority of HCC samples, the levels of pregenomic/precore RNA (pgRNA) and covalently closed circular DNA (cccDNA) were lower than those in liver tissue counterparts...
May 15, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29491156/asymmetric-modification-of-hepatitis-b-virus-hbv-genomes-by-an-endogenous-cytidine-deaminase-inside-hbv-cores-informs-a-model-of-reverse-transcription
#18
Smita Nair, Adam Zlotnick
Cytidine deaminases inhibit replication of a broad range of DNA viruses by deaminating cytidines on single-stranded DNA (ssDNA) to generate uracil. While several lines of evidence have revealed hepatitis B virus (HBV) genome editing by deamination, it is still unclear which nucleic acid intermediate of HBV is modified. Hepatitis B virus has a relaxed circular double-stranded DNA (rcDNA) genome that is reverse transcribed within virus cores from a RNA template. The HBV genome also persists as covalently closed circular DNA (cccDNA) in the nucleus of an infected cell...
May 15, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29463147/comparison-of-hepatitis-b-virus-core-related-antigen-and-hepatitis-b-surface-antigen-for-predicting-hbeag-seroconversion-in-chronic-hepatitis-b-patients-with-pegylated-interferon-therapy
#19
Meng-Lan Wang, Juan Liao, Bing Wei, Dong-Mei Zhang, Ming He, Ming-Chuan Tao, En-Qiang Chen, Hong Tang
AIM: Recent studies revealed that both quantitative hepatitis B surface antigen (qHBsAg) and hepatitis B core-related antigen (qHBcrAg) could serve as a good marker for predicting treatment response and indirectly reflecting intrahepatic cccDNA levels. This study aimed to compare the value of qHBsAg and qHBcrAg in predicting HBeAg seroconversion among patients undergoing PEG-IFN therapy. METHODS: A total of 31 HBeAg-positive patients, who underwent PEG-IFN therapy for 12 months and follow-up for six months were retrospectively included in this study...
February 20, 2018: Infectious Diseases
https://www.readbyqxmd.com/read/29458131/inhibition-of-hepatitis-b-virus-replication-via-hbv-dna-cleavage-by-cas9-from-staphylococcus-aureus
#20
Yu Liu, Miaoxian Zhao, Mingxing Gong, Ying Xu, Cantao Xie, Haohui Deng, Xueying Li, Hongkai Wu, Zhanhui Wang
Chronic hepatitis B virus (HBV) infection is difficult to cure due to the presence of covalently closed circular DNA (cccDNA). Accumulating evidence indicates that the CRISPR/Cas9 system effectively disrupts HBV genome, including cccDNA, in vitro and in vivo. However, efficient delivery of CRISPR/Cas9 system to the liver or hepatocytes using an adeno-associated virus (AAV) vector remains challenging due to the large size of Cas9 from Streptococcus pyogenes (Sp). The recently identified Cas9 protein from Staphylococcus aureus (Sa) is smaller than SpCas9 and thus is able to be packaged into the AAV vector...
April 2018: Antiviral Research
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