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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
#1
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
#2
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...
November 15, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27855500/treatment-of-hepatitis-b-virus-an-update
#3
Haley Ward, Lydia Tang, Bhawna Poonia, Shyam Kottilil
Chronic hepatitis B virus infection is a global health concern as it affects over 240 million people worldwide and an estimated 686,000 people die annually as a result of complications of the disease. With the development of newer antiviral drugs, viral suppression of HBV is achievable, however elimination of HBV from infected individuals (functional cure) remains an issue. Due to persistence of HBV DNA (cccDNA) in infected cells, chronically infected patients who discontinue therapy prior to HBsAg loss or seroconversion are likely to relapse...
December 2016: Future Microbiology
https://www.readbyqxmd.com/read/27819342/minicircle-hbv-cccdna-with-a-gaussia-luciferase-reporter-for-investigating-hbv-cccdna-biology-and-developing-cccdna-targeting-drugs
#4
Feng Li, Liang Cheng, Christopher M Murphy, Natalia J Reszka-Blanco, Yaxu Wu, Liqun Chi, Jianming Hu, Lishan Su
Chronic Hepatitis B Virus (HBV) infection is generally not curable with current anti-viral drugs. Virus rebounds after stopping treatment from the stable HBV covalently-closed-circular DNA (cccDNA). The development of drugs that directly target cccDNA is hampered by the lack of robust HBV cccDNA models. We report here a novel HBV cccDNA technology that will meet the need. We engineered a minicircle HBV cccDNA with a Gaussia Luciferase reporter (mcHBV-GLuc cccDNA), which serves as a surrogate to measure cccDNA activity...
November 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27797587/the-current-status-and-future-directions-of-hepatitis-b-antiviral-drug-discovery
#5
Liudi Tang, Qiong Zhao, Shuo Wu, Junjun Cheng, Jinhong Chang, Ju-Tao Guo
The current standard care of chronic hepatitis B fails to induce a durable off-drug control of hepatitis B virus (HBV) replication in the majority of treated patients. The primary reasons are its inability to eliminate the covalently closed circular (ccc) DNA, the nuclear form of HBV genome, and restoration of the dysfunctional host antiviral immune response against the virus. Accordingly, discovery and development of therapeutics to completely stop HBV replication, eliminate or functionally inactivate cccDNA as well as activate a functional antiviral immune response against HBV are the primary efforts for finding a cure for chronic hepatitis B...
November 11, 2016: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/27793933/apoptosis-of-hepatitis-b-virus-expressing-liver-tumor-cells-induced-by-a-high-concentration-of-nucleos-t-ide-analogue
#6
Eunyoung Tak, Shin Hwang, Han Chu Lee, Gi-Young Ko, Chul-Soo Ahn, Young-In Yoon, Young-Suk Lim, Dae-Young Jun, Ki-Hun Kim, Gi-Won Song, Deog-Bok Moon, Baek-Yeol Ryoo, Nayoung Kim, Sung-Gyu Lee
BACKGROUND/AIM: We investigated the expression of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) and HBV X protein (HBx) in human hepatocellular carcinoma (HCC) and evaluated the effect of high-concentration nucleos(t)ide analogs (NUCs) on liver tumor cell lines. MATERIALS AND METHODS: This study consisted of three parts: part I used human blood and non-tumor liver tissues; part II used human HCC and adjacent liver tissues; and part III used an HBV-expressing liver tumor cell line...
November 2016: Anticancer Research
https://www.readbyqxmd.com/read/27788717/-potential-clinical-significance-of-hbv-rna-virus-like-particle
#7
F M Lu, J Wang, H Zhuang
Our recent studies confirmed that the HBV RNAs present in the serum of chronic hepatitis B(CHB)patients are pregenomic RNAs(pgRNAs)with a size of 3.5 kb. These pgRNAs are located in virus-like particles whose morphological structure is similar to that of Dan particles. Since pgRNAs can only be transcribed from the covalently closed circular DNA(cccDNA)located in the nuclear of infected hepatocytes, and the production of pgRNAs is not affected by nucleos(t)ide analogues(NUCs), the presence of viral RNA in serum can reflect the presence of cccDNA in hepatocytes and its transcriptional activity in patients treated with medication...
September 20, 2016: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/27783675/dna-polymerase-%C3%AE%C2%BA-is-a-key-cellular-factor-for-the-formation-of-covalently-closed-circular-dna-of-hepatitis-b-virus
#8
Yonghe Qi, Zhenchao Gao, Guangwei Xu, Bo Peng, Chenxuan Liu, Huan Yan, Qiyan Yao, Guoliang Sun, Yang Liu, Dingbin Tang, Zilin Song, Wenhui He, Yinyan Sun, Ju-Tao Guo, Wenhui Li
Hepatitis B virus (HBV) infection of hepatocytes begins by binding to its cellular receptor sodium taurocholate cotransporting polypeptide (NTCP), followed by the internalization of viral nucleocapsid into the cytoplasm. The viral relaxed circular (rc) DNA genome in nucleocapsid is transported into the nucleus and converted into covalently closed circular (ccc) DNA to serve as a viral persistence reservoir that is refractory to current antiviral therapies. Host DNA repair enzymes have been speculated to catalyze the conversion of rcDNA to cccDNA, however, the DNA polymerase(s) that fills the gap in the plus strand of rcDNA remains to be determined...
October 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27771387/hdv-rna-replication-is-associated-with-hbv-repression-and-interferon-stimulated-genes-induction-in-super-infected-hepatocytes
#9
Dulce Alfaiate, Julie Lucifora, Natali Abeywickrama-Samarakoon, Maud Michelet, Barbara Testoni, Jean-Claude Cortay, Camille Sureau, Fabien Zoulim, Paul Dény, David Durantel
Hepatitis D virus (HDV) super-infection of Hepatitis B virus (HBV)-infected patients is the most aggressive form of viral hepatitis. HDV infection is not susceptible to direct anti-HBV drugs, and only suboptimal antiviral responses are obtained with interferon (IFN)-alpha-based therapy. To get insights on HDV replication and interplay with HBV in physiologically relevant hepatocytes, differentiated HepaRG (dHepaRG) cells, previously infected or not with HBV, were infected with HDV, and viral markers were extensively analyzed...
October 19, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27761441/hepatitis-b-progress-in-understanding-chronicity-the-innate-immune-response-and-cccdna-protection
#10
REVIEW
Kenichi Morikawa, Tomoe Shimazaki, Rei Takeda, Takaaki Izumi, Machiko Umumura, Naoya Sakamoto
Hepatitis B virus (HBV) infection is a serious health threat around the world. Despite the availability of an effective hepatitis B vaccine, the number of HBV carriers is estimated to be as high as 240 million worldwide. Global mortality due to HBV-related liver diseases such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC) may be as high as 1 million deaths per year. HBV is transmitted via blood and body fluids, and is much more infectious than both human immunodeficiency virus (HIV) and hepatitis C virus...
September 2016: Annals of Translational Medicine
https://www.readbyqxmd.com/read/27746336/human-stem-cell-derived-hepatocytes-as-a-model-for-hepatitis-b-virus-infection-spreading-and-virus-host-interactions
#11
Yuchen Xia, Arnaud Carpentier, Xiaoming Cheng, Peter Daniel Block, Yao Zhao, Zhensheng Zhang, Ulrike Protzer, T Jake Liang
BACKGROUND & AIMS: One major obstacle of hepatitis B virus (HBV) research is the lack of efficient cell culture system permissive for viral infection and replication. The aim of our study was to establish a robust HBV infection model by using hepatocyte-like cells (HLCs) derived from human pluripotent stem cells. METHODS: HLCs were differentiated from human embryonic stem cells and induced pluripotent stem cells. Maturation of hepatocyte functions was determined...
October 14, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/27739230/safety-tolerability-and-pharmacokinetics-of-arc-520-injection-an-rna-interference-based-therapeutic-for-the-treatment-of-chronic-hepatitis-b-virus-infection-in-healthy-volunteers
#12
Thomas Schluep, Jason Lickliter, James Hamilton, David L Lewis, Ching-Lung Lai, Johnson Yn Lau, Stephen A Locarnini, Robert G Gish, Bruce D Given
ARC-520 Injection, an RNA interference drug for the treatment of hepatitis B that targets cccDNA-derived viral mRNA transcripts with high specificity, effectively reduces the production of viral proteins and HBV DNA. In this phase I, randomized, double-blind, placebo-controlled study, 54 healthy volunteers (half male, half female) received a single, intravenous dose of 0.01-4.0 mg/kg ARC-520 Injection (N = 36) or placebo (N = 18). Assessments included safety, tolerability, pharmacokinetics, and pharmacodynamics (cytokines and complement)...
October 14, 2016: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/27686728/quantitative-intrahepatic-hbv-cccdna-correlates-with-histological-liver-inflammation-in-chronic-hepatitis-b-virus-infection
#13
Ling-Bo Liang, Xia Zhu, Li-Bo Yan, Ling-Yao Du, Cong Liu, Juan Liao, Hong Tang
BACKGROUND: The aim of this study was to determine the role of baseline hepatitis B virus (HBV) forming covalently closed circular DNA (HBV cccDNA) in liver inflammation in patients infected with HBV with serum alanine aminotransferase (ALT) levels under two times the upper limit of normal (2×ULN). METHODS: After liver biopsy and serum virological and biochemical marker screening, patients diagnosed with chronic HBV infection with serum ALT levels under 2×ULN and histological liver inflammation of less than grade G2 were prospectively recruited into this study...
September 26, 2016: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/27659023/highly-multiplexed-crispr-cas9-nuclease-and-cas9-nickase-vectors-for-inactivation-of-hepatitis-b-virus
#14
Tetsushi Sakuma, Keiichi Masaki, Hiromi Abe-Chayama, Keiji Mochida, Takashi Yamamoto, Kazuaki Chayama
CRISPR-Cas9-mediated genome-editing technology contributes not only to basic genomic studies but also to clinical studies such as genetic correction and virus inactivation. Hepatitis B virus (HBV) is a major target for potential application of CRISPR-Cas9 in eliminating viral DNA from human cells. However, the high stability of covalently closed circular DNA (cccDNA) makes it difficult to completely clear HBV infection. Here, we report highly multiplexed CRISPR-Cas9-nuclease and Cas9-nickase vector systems that simultaneously target three critical domains of the HBV genome...
November 2016: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/27639844/reduction-of-covalently-closed-circular-dna-with-long-term-nucleos-t-ide-analogue-treatment-in-chronic-hepatitis-b
#15
Ching-Lung Lai, Danny Wong, Philip Ip, Malgorzata Kopaniszen, Wai-Kay Seto, James Fung, Fung-Yu Huang, Brian Lee, Giuseppe Cullaro, Chun Kong Chong, Ringo Wu, Charles Cheng, John Yuen, Vincent Ngai, Man-Fung Yuen
BACKGROUND AND AIMS: Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA), a mini-chromosome essential for HBV replication, is supposed to be resistant to nucleos(t)ide analogue treatment. We investigated the effect of long-term nucleos(t)ide analogue treatment on cccDNA. METHODS: Among 129 patients who had been enrolled in previous international nucleos(t)ide analogue clinical trials and had liver biopsies at baseline and one year after treatment, we recruited 43 patients on long-term continuous treatment for 72 to 145months for a third liver biopsy...
September 14, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/27639371/antiviral-strategies-to-eliminate-hepatitis-b-virus-covalently-closed-circular-dna-cccdna
#16
Peter Revill, Stephen Locarnini
It has been over 50 years since the discovery of hepatitis B virus (HBV), yet 240 million people worldwide live with chronic HBV, resulting in up to 800000 deaths per year. A cure is yet to be achieved, due largely to a viral nuclear reservoir of transcriptionally active covalently closed circular DNA (cccDNA). While current antiviral therapies are effective at reducing viral replication, they have no impact on the existing cccDNA reservoir. Identifying mechanisms to either eliminate (complete cure) or inactivate (functional cure) HBV cccDNA are a major focus of HBV research worldwide...
September 15, 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27639252/hepatitis-b-virus-x-protein-crosses-out-smc5-6-complex-to-maintain-covalently-closed-circular-dna-transcription
#17
EDITORIAL
Bidisha Mitra, Haitao Guo
No abstract text is available yet for this article.
December 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27626656/hepatitis-b-virus-x-protein-promotes-degradation-of-smc5-6-to-enhance-hbv-replication
#18
Christopher M Murphy, Yanping Xu, Feng Li, Kouki Nio, Natalia Reszka-Blanco, Xiaodong Li, Yaxu Wu, Yanbao Yu, Yue Xiong, Lishan Su
The hepatitis B virus (HBV) regulatory protein X (HBx) activates gene expression from the HBV covalently closed circular DNA (cccDNA) genome. Interaction of HBx with the DDB1-CUL4-ROC1 (CRL4) E3 ligase is critical for this function. Using substrate-trapping proteomics, we identified the structural maintenance of chromosomes (SMC) complex proteins SMC5 and SMC6 as CRL4(HBx) substrates. HBx expression and HBV infection degraded the SMC5/6 complex in human hepatocytes in vitro and in humanized mice in vivo. HBx targets SMC5/6 for ubiquitylation by the CRL4(HBx) E3 ligase and subsequent degradation by the proteasome...
September 13, 2016: Cell Reports
https://www.readbyqxmd.com/read/27610013/roles-of-hepatocyte-nuclear-factors-in-hepatitis-b-virus-infection
#19
REVIEW
Doo Hyun Kim, Hong Seok Kang, Kyun-Hwan Kim
Approximately 350 million people are estimated to be persistently infected with hepatitis B virus (HBV) worldwide. HBV maintains persistent infection by employing covalently closed circular DNA (cccDNA), a template for all HBV RNAs. Chronic hepatitis B (CHB) patients are currently treated with nucleos(t)ide analogs such as lamivudine, adefovir, entecavir, and tenofovir. However, these treatments rarely cure CHB because they are unable to inhibit cccDNA transcription and inhibit only a late stage in the HBV life cycle (the reverse transcription step in the nucleocapsid)...
August 21, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27603796/activating-the-innate-immune-response-to-counter-chronic-hepatitis-b-virus-infection
#20
Camilla Lamb, Patrick Arbuthnot
INTRODUCTION: Chronic infection with hepatitis B virus (HBV) is endemic to several populous parts of the world, where resulting complicating cirrhosis and hepatocellular carcinoma occur commonly. Licensed drugs to treat the infection have limited curative efficacy, and development of therapies that eliminate all replication intermediates of HBV is a priority. AREAS COVERED: The recent demonstration that the activation of the innate immune response may eradicate HBV from infected hepatocytes has a promising therapeutic application...
September 7, 2016: Expert Opinion on Biological Therapy
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