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https://www.readbyqxmd.com/read/28213165/hbvcircle-a-novel-tool-to-investigate-hepatitis-b-virus-covalently-closed-circular-dna
#1
Zhipeng Yan, Jing Zeng, Youjun Yu, Kunlun Xiang, Hui Hu, Xue Zhou, Lili Gu, Li Wang, Jie Zhao, John A T Young, Lu Gao
BACKGROUND & AIMS: Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) persists as a stable episome in infected hepatocytes and serves as a template for the transcription of all viral genes. Due to the narrow host range of HBV, the development of a robust mouse model that supports cccDNA-dependent viral replication is a key hurdle in the development of novel HBV therapeutics. This study aimed to develop a novel tool to investigate HBV cccDNA. METHODS: Through minicircle technology, HBVcircle, a recombinant cccDNA, was easily generated and extracted from a genetically engineered E...
February 14, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28212627/genome-wide-identification-of-direct-hbx-genomic-targets
#2
Francesca Guerrieri, Laura Belloni, Daniel D'Andrea, Natalia Pediconi, Loredana Le Pera, Barbara Testoni, Cecilia Scisciani, Oceane Floriot, Fabien Zoulim, Anna Tramontano, Massimo Levrero
BACKGROUND: The Hepatitis B Virus (HBV) HBx regulatory protein is required for HBV replication and involved in HBV-related carcinogenesis. HBx interacts with chromatin modifying enzymes and transcription factors to modulate histone post-translational modifications and to regulate viral cccDNA transcription and cellular gene expression. Aiming to identify genes and non-coding RNAs (ncRNAs) directly targeted by HBx, we performed a chromatin immunoprecipitation sequencing (ChIP-Seq) to analyse HBV recruitment on host cell chromatin in cells replicating HBV...
February 17, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28195359/sodium-taurocholate-cotransporting-polypeptide-is-the-limiting-host-factor-of-hepatitis-b-virus-infection-in-macaque-and-pig-hepatocytes
#3
Florian A Lempp, Ellen Wiedtke, Bingqian Qu, Pierre Roques, Isabelle Chemin, Florian W R Vondran, Roger Le Grand, Dirk Grimm, Stephan Urban
: Infections with the human Hepatitis B (HBV) and Hepatitis D Virus (HDV) depend on species-specific host factors like the receptor human sodium taurocholate cotransporting polypeptide hNTCP. Complementation of mouse hepatocytes with hNTCP confers susceptibility to HDV but not HBV indicating the requirement of additional HBV-specific factors. As an essential premise towards the establishment for an HBV-susceptible animal model, we investigated the role of hNTCP as a limiting factor of hepatocytes in commonly used laboratory animals...
February 13, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28182305/hepatitis-b-virus-covalently-closed-circular-dna-homeostasis-is-independent-of-the-lymphotoxin-pathway-during-chronic-hbv-infection
#4
Marie-Anne Meier, Aleksei Suslov, Sylvia Ketterer, Markus H Heim, Stefan F Wieland
Current treatment options for patients with chronic hepatitis B virus (HBV) infection are not curative as they are not effective in eliminating covalently closed circular DNA (cccDNA). cccDNA is a stable template for HBV transcription in the nucleus of hepatocytes and is thought to be one of the main factors responsible for HBV persistence. Recently, activation of the lymphotoxin beta receptor (LTβR) has been shown to trigger degradation of cccDNA through induction of cytidine deaminases of the APOBEC3 family in HBV cell culture model systems...
February 9, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/28121714/hepatitis-delta-and-hiv-infection
#5
Vincent Soriano, Kenneth E Sherman, Pablo Barreiro
Viral liver diseases are frequent co-morbidities and major contributors to death in HIV-positive individuals on antiretroviral therapy. Whereas cure of hepatitis C and control of hepatitis B with antivirals avert liver disease progression in most HIV-coinfected patients, the lack of satisfactory treatment for hepatitis delta virus (HDV) infection remains a major threat for developing cirrhosis and liver cancer in this population. In the European Union and North America, sexual contact has replaced injection drug use has major transmission route for HDV in HIV-positive persons...
January 24, 2017: AIDS
https://www.readbyqxmd.com/read/28095508/the-smc5-6-complex-restricts-hbv-when-localized-to-nd10-without-inducing-an-innate-immune-response-and-is-counteracted-by-the-hbv-x-protein-shortly-after-infection
#6
Congrong Niu, Christine M Livingston, Li Li, Rudolf K Beran, Stephane Daffis, Dhivya Ramakrishnan, Dara Burdette, Leanne Peiser, Eduardo Salas, Hilario Ramos, Mei Yu, Guofeng Cheng, Michel Strubin, William E Delaney Iv, Simon P Fletcher
The structural maintenance of chromosome 5/6 complex (Smc5/6) is a restriction factor that represses hepatitis B virus (HBV) transcription. HBV counters this restriction by expressing HBV X protein (HBx), which targets Smc5/6 for degradation. However, the mechanism by which Smc5/6 suppresses HBV transcription and how HBx is initially expressed is not known. In this study we characterized viral kinetics and the host response during HBV infection of primary human hepatocytes (PHH) to address these unresolved questions...
2017: PloS One
https://www.readbyqxmd.com/read/28087399/advances-with-using-crispr-cas-mediated-gene-editing-to-treat-infections-with-hepatitis-b-virus-and-hepatitis-c-virus
#7
REVIEW
Buhle Moyo, Kristie Bloom, Tristan Scott, Abdullah Ely, Patrick Arbuthnot
Chronic infections with hepatitis B and hepatitis C viruses (HBV and HCV) account for the majority of cases of cirrhosis and hepatocellular carcinoma. Current therapies for the infections have limitations and improved efficacy is necessary to prevent complications in carriers of the viruses. In the case of HBV persistence, the replication intermediate comprising covalently closed circular DNA (cccDNA) is particularly problematic. Licensed therapies have little effect on cccDNA and HBV replication relapses following treatment withdrawal...
January 10, 2017: Virus Research
https://www.readbyqxmd.com/read/28052637/future-anti-hbv-strategies
#8
REVIEW
Edward J Gane
Although current oral antivirals can maintain viral suppression and reduce the risk of liver-related complications, lifelong therapy is associated with high cost, risk of breakthrough and potential toxicity. There is a need to develop a finite course of treatment which can provide sustained off-treatment virological and clinical response. The likely marker of such a clinical HBV CURE would be HBsAg clearance, but in addition cccDNA elimination would be required to prevent future reactivation (ie complete HBV cure)...
January 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28052622/novel-targets-for-hepatitis-b-virus-therapy
#9
REVIEW
Barbara Testoni, David Durantel, Fabien Zoulim
Treatment with either pegylated interferon-alpha (pegIFN-α) or last generation nucleos(t)ide analogues (NAs) successfully leads to serum viral load suppression in most chronically infected hepatitis B (CHB) patients, but HBsAg loss is only achieved in 10% of the cases after a 5-year follow-up. Thus, therapy must be administered long-term and it will not completely eliminate infection because of the persistent hepatitis B virus (HBV) minichromosome in infected cells, and cannot completely abolish the risk of developing severe sequelae such as cirrhosis and hepatocellular carcinoma...
January 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/27998270/pcr-mediated-recombination-impacts-the-analysis-of-hepatitis-b-virus-covalently-closed-circular-dna
#10
Rodolphe Suspène, Valérie Thiers, Jean-Pierre Vartanian, Simon Wain-Hobson
BACKGROUND: The replication of HBV involves the production of covalently closed circular DNA (cccDNA) from the HBV genome through the repair of virion relaxed circular DNA (rcDNA) in the virion. As cccDNA is the transcription template for HBV genomes, it needs to be eliminated from hepatocytes if the eradication of chronic HBV infection is to be achieved. PCR quantitation of cccDNA copy number is the technique of choice for evaluating the efficiency of treatment regimens. The PCR target commonly used to identify cccDNA spans the gapped region of rcDNA and is considered to accurately distinguish between cccDNA and rcDNA...
December 20, 2016: Retrovirology
https://www.readbyqxmd.com/read/27992681/hepatitis-b-virus-core-related-antigen-as-a-surrogate-marker-for-covalently-closed-circular-dna
#11
Danny Ka-Ho Wong, Wai-Kay Seto, Ka-Shing Cheung, Chun-Kong Chong, Fung-Yu Huang, James Fung, Ching-Lung Lai, Man-Fung Yuen
BACKGROUND & AIMS: Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) is a key to viral persistence in chronic hepatitis B infection. Serum hepatitis B core-related antigen (HBcrAg) is a novel marker for HBV disease. We aimed to determine whether HBcrAg could be a surrogate marker for intrahepatic cccDNA. METHODS: Three hundred and five liver biopsies and the corresponding sera collected from 138 nucleos(t)ide analogues-treated patients were analysed...
December 19, 2016: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/27978466/metabolite-identification-of-bentysrepinine-y101-a-novel-anti-hbv-agent-in-rats-using-a-five-step-strategy-based-on-a-combined-workflow-with-two-different-platforms-of-liquid-chromatography-tandem-mass-spectrometry
#12
Huirong Fan, Zhanxing Hu, Ruixing Li, Shiqi Dong, Yuan Gu, Ting Liu, Duanyun Si, Guangyi Liang, Changxiao Liu
Bentysrepinine (Y101), a derivative of repensine (a compound isolated from Dichondrarepens Forst), is a novel phenyalanine dipeptide inhibiting DNA-HBV and cccDNA activities and is currently under development for the treatment of hepatitis B virus (HBV)-infected hepatitis. Our previous study implied that there might be an existence of extensive metabolism of Y101 in rats. Therefore, it is necessary to perform metabolic profiling study to further evaluate its safety and drug-like properties. In this study, the metabolism of Y101 in rats was investigated by a convincible five-step strategy to characterize metabolites in plasma and that excreted into urine, bile and feces...
January 1, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/27975313/immunofluorescent-staining-for-the-detection-of-the-hepatitis-b-core-antigen-in-frozen-liver-sections-of-human-liver-chimeric-mice
#13
Lena Allweiss, Marc Lütgehetmann, Maura Dandri
The hepatitis B virus (HBV) is the causative agent for chronic hepatitis B infection, which affects an estimate of 240 million people worldwide and puts them at risk of developing terminal liver disease. The life cycle of the virus and its interactions with the host immune system are still incompletely understood, and currently available treatment options rarely achieve a cure. Therefore, basic research and new drug development are needed. One parameter for measuring the intrahepatic activity of the virus is monitoring the production of the HBV core antigen (HBcAg), which not only serves as the main structural protein of its nucleocapsid but is also recruited to the covalently closed circular DNA (cccDNA), the nuclear HBV genome responsible for infection persistence...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27975310/a-t7-endonuclease-i-assay-to-detect-talen-mediated-targeted-mutation-of-hbv-cccdna
#14
Kristie Bloom, Abdullah Ely, Patrick Arbuthnot
Gene editing using designer nucleases is now widely used in many fields of molecular biology. The technology is being developed for the treatment of viral infections such as persistant hepatitis B virus (HBV). The replication intermediate of HBV comprising covalently closed circular DNA (cccDNA) is stable and resistant to available licensed antiviral agents. Advancing gene editing as a means of introducing targeted mutations into cccDNA thus potentially offers the means to cure infection by the virus. Essentially, targeted mutations are initiated by intracellular DNA cleavage, then error-prone nonhomologous end joining results in insertions and deletions (indels) at intended sites...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27975309/detection-of-hbv-cccdna-methylation-from-clinical-samples-by-bisulfite-sequencing-and-methylation-specific-pcr
#15
Yongmei Zhang, Richeng Mao, Haitao Guo, Jiming Zhang
Mapping of DNA methylation is essential in understanding the process of HBV covalently closed circular DNA (cccDNA) transcription. Here, bisulfite sequencing PCR and methylation-specific PCR, two PCR-based approaches used in determining and quantifying the DNA methylation pattern, are described.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27975308/analyses-of-hbv-cccdna-quantification-and-modification
#16
Yuchen Xia, Daniela Stadler, Chunkyu Ko, Ulrike Protzer
Covalently closed circular DNA (cccDNA) serves as the transcriptional template of hepatitis B virus (HBV) replication in the nucleus of infected cells. It ensures the persistence of HBV even if replication is blocked. Immune-mediated killing of infected hepatocytes, cell division, or cytokine induced non-cytolytic degradation of cccDNA can induce the loss of cccDNA. For studies on HBV control, the analysis of cccDNA integrity and its exact quantification is very important. Here, we describe different methods for HBV cccDNA quantification and modification...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27975303/ntcp-reconstituted-in-vitro-hbv-infection-system
#17
Yinyan Sun, Yonghe Qi, Bo Peng, Wenhui Li
Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a functional receptor for hepatitis B virus (HBV). Expressing human NTCP in human hepatoma HepG2 cells (HepG2-NTCP) renders these cells susceptible for HBV infection. The HepG2-NTCP stably transfected cell line provides a much-needed and easily accessible platform for studying the virus. HepG2-NTCP cells could also be used to identify chemicals targeting key steps of the virus life cycle including HBV covalent closed circular (ccc) DNA, and enable the development of novel antivirals against the infection...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27968847/bushenjianpi-formula-combined-with-entecavir-for-hbeag-negative-chronic-hepatitis-b-patients-a-multicentre-randomised-double-blind-placebo-controlled-trial
#18
Yue-Qiu Gao, Xin Zhang, Man Li, Zhen-Hua Zhou, Xue-Hua Sun, Xiao-Jun Zhu, Shu-Gen Jin
BACKGROUND: The treatment combination of traditional Chinese medicine with western medicine results in significant decrease of serum hepatitis B virus (HBV) DNA and increase of HBeAg loss in patients with HBeAg-positive chronic hepatitis B (CHB) without any serious adverse events. We aimed to assess whether the Bushenjianpi Formula combined with entecavir could increase the HBsAg loss rate in patients with HBeAg-negative CHB. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, we recruited patients with HBeAg-negative CHB from ten third-level grade-A hospital of Traditional Chinese Medicine...
October 2016: Lancet
https://www.readbyqxmd.com/read/27882060/simple-and-reliable-method-to-quantify-the-hepatitis-b-viral-load-and-replicative-capacity-in-liver-tissue-and-blood-leukocytes
#19
Claudia Minosse, Sabrina Coen, Ubaldo Visco Comandini, Raffaella Lionetti, Marzia Montalbano, Stefano Cerilli, Donatella Vincenti, Andrea Baiocchini, Maria R Capobianchi, Stefano Menzo
BACKGROUND: A functional cure of chronic hepatitis B (CHB) is feasible, but a clear view of the intrahepatic viral dynamics in each patient is needed. Intrahepatic covalently closed circular DNA (cccDNA) is the stable form of the viral genome in infected cells, and represents the ideal marker of parenchymal colonization. Its relationships with easily accessible peripheral parameters need to be elucidated in order to avoid invasive procedures in patients. OBJECTIVES: The goal of this study was to design, set up, and validate a reliable and straightforward method for the quantification of the cccDNA and total DNA of the hepatitis B virus (HBV) in a variety of clinical samples...
October 2016: Hepatitis Monthly
https://www.readbyqxmd.com/read/27864147/host-factor-prpf31-is-involved-in-cccdna-production-in-hbv-replicating-cells
#20
Wataru Kinoshita, Naoki Ogura, Koichi Watashi, Takaji Wakita
Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) plays a central role in chronic HBV infection and replication, and is an important factor for HBV surface antigen loss indicating the endpoint of HBV treatment. However, there is a known problem that current anti-HBV drugs, including interferons and nucleos(t)ide analogues, reduce HBV replication but have a little or no effect on reducing cccDNA. Therefore, the development of new therapeutic agents is necessary to eradicate cccDNA. In this study, we identified pre-mRNA processing factor 31 (PRPF31) by siRNA screening as a factor associated with cccDNA...
January 22, 2017: Biochemical and Biophysical Research Communications
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