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HBV core protein

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https://www.readbyqxmd.com/read/28635671/rab33b-controls-hepatitis-b-virus-assembly-by-regulating-core-membrane-association-and-nucleocapsid-processing
#1
Christina Bartusch, Tatjana Döring, Reinhild Prange
Many viruses take advantage of cellular trafficking machineries to assemble and release new infectious particles. Using RNA interference (RNAi), we demonstrate that the Golgi/autophagosome-associated Rab33B is required for hepatitis B virus (HBV) propagation in hepatoma cell lines. While Rab33B is dispensable for the secretion of HBV subviral envelope particles, its knockdown reduced the virus yield to 20% and inhibited nucleocapsid (NC) formation and/or NC trafficking. The overexpression of a GDP-restricted Rab33B mutant phenocopied the effect of deficit Rab33B, indicating that Rab33B-specific effector proteins may be involved...
June 21, 2017: Viruses
https://www.readbyqxmd.com/read/28628133/hbv-rna-pre-genome-encodes-specific-motifs-that-mediate-interactions-with-the-viral-core-protein-that-promote-nucleocapsid-assembly
#2
Nikesh Patel, Simon J White, Rebecca F Thompson, Richard Bingham, Eva U Weiß, Daniel P Maskell, Adam Zlotnick, Eric C Dykeman, Roman Tuma, Reidun Twarock, Neil A Ranson, Peter G Stockley
Formation of the hepatitis B virus nucleocapsid is an essential step in the viral lifecycle, but its assembly is not fully understood. We report the discovery of sequence-specific interactions between the viral pre-genome and the hepatitis B core protein that play roles in defining the nucleocapsid assembly pathway. Using RNA SELEX and bioinformatics, we identified multiple regions in the pre-genomic RNA with high affinity for core protein dimers. These RNAs form stem-loops with a conserved loop motif that trigger sequence-specific assembly of virus-like particles (VLPs) at much higher fidelity and yield than in the absence of RNA...
June 19, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28611266/retinoid-x-receptor-%C3%AE-dependent-hbv-minichromosome-remodeling-and-viral-replication
#3
Yan Zhang, Song He, Jin-Jun Guo, Hong Peng, Jia-Hao Fan, Qing-Ling Li
BACKGROUND AND AIM: The HBV covalently closed circular DNA (cccDNA) is organized into a minichromosome in the nuclei of infected hepatocytes through interactions with histone and nonhistone proteins. Retinoid X receptor α (RXRα), a liver-enriched nuclear receptor, participates in regulation of HBV replication and transcription through modulation of HBV enhancer 1 and core promoter activity. MATERIAL AND METHODS: This study investigated RXRα involvement in HBV cccDNA epigenetic modifications...
August 1, 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28584639/the-evaluation-of-fibrotic-effects-of-the-hepatitis-b-virus-pre-core-in-hepatic-stellate-cells
#4
Seyed Younes Hosseini, Kazem Baesi, Negar Azarpira, Ameneh Pakneiat, Seyedeh Akram Hosseini
The role of the hepatitis B virus (HBV) endogenous pre-core protein in liver fibrosis is controversial. Whether the expression of the pre-core induces the activation of human stellate cells (HSCs) has not yet been reported. Plasmids expressing HBx, or pre-core protein were transfected into LX-2 cells. Subsequently, total RNA extracted and reverse transcription-quantitative polymerase chain reaction was performed to measure the fold change of collagen type I, α1 chain, α-smooth muscle actin and TIMP metalloproteinase inhibitor-1...
June 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28584155/capsid-assembly-modulators-have-a-dual-mechanism-of-action-in-primary-human-hepatocytes-infected-with-hepatitis-b-virus
#5
Jan Martin Berke, Pascale Dehertogh, Karen Vergauwen, Ellen van Damme, Wendy Mostmans, Koen Vandyck, Frederik Pauwels
Hepatitis B Virus (HBV) capsid assembly is a critical step in the propagation of the virus mediated by the core protein. Due to its multiple functions in the viral life cycle, core became an attractive target for new antiviral therapies. Capsid assembly modulators (CAMs) accelerate the kinetics of capsid assembly and prevent encapsidation of the polymerase-pregenomic RNA (pol-pgRNA) complex thereby blocking viral replication. CAM JNJ-632 is a novel and potent inhibitor of HBV replication in vitro across genotypes A-D...
June 5, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28584057/an-rnai-based-high-throughput-screening-assay-to-identify-small-molecule-inhibitors-of-hepatitis-b-virus-replication
#6
Subhanita Ghosh, Abhinav Kaushik, Sachin Khurana, Aditi Varshney, Avishek Kumar Singh, Pradeep Dahiya, Jitendra K Thakur, Shiv Kumar Sarin, Dinesh Gupta, Pawan Malhotra, Sunil K Mukherjee, Raj K Bhatnagar
Persistent or chronic infection with the hepatitis B virus represents one of the most common viral diseases in humans. The hepatitis B virus deploys the Hepatitis B Virus X Protein (HBx) as a suppressor of host defenses consisting of RNAi-based silencing of viral genes. Because of its critical role in countering host defenses, HBx represents an attractive target for antiviral drugs. Here, we developed and optimized a loss-of-function screening procedure, which identified a potential pharmacophore that abrogated HBxs RNAi suppression activity...
June 5, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28566379/discovery-and-mechanistic-study-of-benzamide-derivatives-that-modulate-hepatitis-b-virus-capsid-assembly
#7
Shuo Wu, Qiong Zhao, Pinghu Zhang, John Kulp, Lydia Hu, Nicky Hwang, Jiming Zhang, Timothy M Block, Xiaodong Xu, Yanming Du, Jinhong Chang, Ju-Tao Guo
Chronic hepatitis B virus (HBV) infection is a global public health problem. Although the currently approved medications can reliably reduce the viral load and prevent the progression of liver diseases, they fail to cure the viral infection. In an effort toward discovery of novel antiviral agents against HBV, a group of benzamide (BA) derivatives that significantly reduced the amount of cytoplasmic HBV DNA were discovered. The initial lead optimization efforts identified two BA derivatives with improved antiviral activity for further mechanistic studies...
May 31, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28559265/hbv-capsid-assembly-modulators-but-not-nucleoside-analogs-inhibit-the-production-of-extracellular-pregenomic-rna-and-spliced-rna-variants
#8
Angela M Lam, Suping Ren, Christine Espiritu, Mollie Kelly, Vincent Lau, Lingjie Zheng, George D Hartman, Osvaldo A Flores, Klaus Klumpp
The Hepatitis B virus (HBV) core protein serves multiple essential functions in the viral life cycle and is being developed as a target for antiviral agents. Capsid assembly modulators (CAMs) are compounds that target core and misdirect capsid assembly, resulting in the suppression of HBV replication and virion production. Besides HBV DNA, circulating HBV RNA has been detected in patient serum and can be associated with treatment response. Here we studied the effect of HBV CAMs on the production of extracellular HBV RNA using infected HepaRG cells and primary human hepatocytes...
May 30, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28499864/role-of-hepatitis-b-core-protein-in-hbv-transcription-and-recruitment-of-histone-acetyltransferases-to-cccdna-minichromosome
#9
Chun Kong Chong, Ching Yan Serene Cheng, Sin Yi Jasmine Tsoi, Fung-Yu Huang, Fen Liu, Wai-Kay Seto, Ching-Lung Lai, Man-Fung Yuen, Danny Ka-Ho Wong
The hepatitis B core protein (HBc) has been suggested to interact with covalently closed circular DNA (cccDNA) and regulate hepatitis B virus (HBV) transcription. However, direct evidence is lacking. We aimed to identify the specific HBc region(s) responsible for transcription regulation and its interaction with cccDNA. Seventeen mutants with mutations at the four arginine-rich clusters of the HBc carboxyl-terminal domain (CTD) were created. The effect of HBc mutations on the levels of HBV DNA, RNA, and hepatitis B surface antigen (HBsAg) were measured...
May 10, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28469174/allosteric-conformational-changes-of-human-hbv-core-protein-transform-its-assembly
#10
Chuang Liu, Guizhen Fan, Zhao Wang, Hong-Song Chen, Chang-Cheng Yin
Hepatitis B Virus core protein (HBc) has multiple roles in the viral lifecycle: viral assembly, compartment for reverse transcription, intracellular trafficking, and nuclear functions. HBc displays assembly polymorphism - it can assemble into icosahedral capsid and aberrant non-capsid structures. It has been hypothesized that the assembly polymorphism is due to allosteric conformational changes of HBc dimer, the smallest assembly unit, however, the mechanism governing the polymorphic assembly of the HBc dimer is still elusive...
May 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28445592/polo-like-kinase-1-is-a-proviral-host-factor-for-hepatitis-b-virus-replication
#11
Ahmed M Diab, Adrien Foca, Floriane Fusil, Thomas Lahlali, Pascal Jalaguier, Fouzia Amirache, Lia N'Guyen, Nathalie Isorce, François-Loïc Cosset, Fabien Zoulim, Ourania M Andrisani, David Durantel
Chronic Hepatitis B Virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC) and current treatments for CHB and HCC are perfectible. Herein, we identified cellular Serine/Threonine Polo-like-kinase 1 (PLK1) as a positive effector of HBV replication. The aim of this study was to demonstrate the proviral role of PLK1 in HBV biosynthesis and validate PLK1 inhibition a potential antiviral strategy. To this end, we employed physiologically relevant HBV infection models of Primary Human Hepatocytes (PHH) and differentiated HepaRG cells, in conjunction with pharmacologic PLK1 inhibitors, siRNA-mediated knockdown, and overexpression of constitutively active PLK1 (PLK1(CA) )...
April 26, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28401569/influences-on-viral-replication-and-sensitivity-to-gls4-a-hap-compound-of-naturally-occurring-t109-v124-mutations-in-hepatitis-b-virus-core-protein
#12
Jianghua Wang, Haiying Zhang, Yingjun Zhang, Dong Jiang, Jing Li, Siegfried Goldmann, Qingyun Ren, Ran Fei, Xueyan Wang, Lai Wei
Heteroaryldihydropyrimidine (HAP) compounds inhibit HBV replication by binding to a hydrophobic pocket at the interface between hepatitis B virus core protein (HBcAg) dimer, which interrupts capsid assembly by changing the kinetics and thermodynamics during this process. Structure biological studies have identified several amino acids in HBcAg crucial for compound binding. Here, we investigated the polymorphisms of T109 and V124 amino acids in HBV sequences submitted to GenBank database. Naturally occurring T109 and V124 and/or possible compensatory mutations in neighbored amino acids were introduced into HBV-expressing plasmids...
April 12, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28396718/characteristics-of-escape-mutations-from-occult-hepatitis-b-virus-infected-patients-with-hematological-malignancies-in-south-egypt
#13
Abeer Elkady, Sayuki Iijima, Sahar Aboulfotuh, Elsayed Mostafa Ali, Douaa Sayed, Nashwa M Abdel-Aziz, Amany M Ali, Shuko Murakami, Masanori Isogawa, Yasuhito Tanaka
AIM: To investigate the prevalence and virological characteristics of occult hepatitis B virus (HBV) infections in patients with hematological malignancies in South Egypt. METHODS: Serum samples were collected from 165 patients with hematological malignancies to monitor titers of HBV DNA, hepatitis B surface antigen (HBsAg), and antibodies to HBV core (anti-HBc) and surface antigens. Serum samples negative for HBsAg and positive for anti-HBc were subjected to nucleic acid extraction and HBV DNA detection by real-time polymerase chain reaction...
March 28, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28373061/sequence-analysis-and-functional-characterization-of-full-length-hepatitis-b-virus-genomes-from-korean-cirrhotic-patients-with-or-without-liver-cancer
#14
Huailiang Zhou, Dina Gewaily, Sang Hoon Ahn, Carina Preskill, Yongxiang Wang, Li Zong, Jing Zhang, Kwang-Hyub Han, Jack Wands, Jisu Li, Shuping Tong
This study aimed to identify and characterize mutations in the hepatitis B virus (HBV) genome associated with advanced liver diseases. The 3.2-kb HBV genome of the C2 subgenotype was amplified from sera of 18 cirrhotic Korean patients with (10) or without (8) hepatocellular carcinoma (HCC), and two clones per patient were characterized by transient transfection experiments in human hepatoma cells. While A1762T/G1764A core promoter mutations were highly prevalent in both groups, the G1896A precore mutation to abolish hepatitis B e antigen (HBeAg) expression was more common in HCC clones (55% vs...
April 1, 2017: Virus Research
https://www.readbyqxmd.com/read/28350327/the-envelope-gene-of-hepatitis-b-virus-is-implicated-in-both-differential-virion-secretion-and-genome-replication-capacities-between-genotype-b-and-genotype-c-isolates
#15
Haodi Jia, Yanli Qin, Chaoyang Chen, Fei Zhang, Cheng Li, Li Zong, Yongxiang Wang, Jiming Zhang, Jisu Li, Yumei Wen, Shuping Tong
Chronic infection by hepatitis B virus (HBV) genotype C is associated with a prolonged replicative phase and an increased risk of liver cancer, compared with genotype B infection. We previously found lower replication capacity but more efficient virion secretion by genotype C than genotype B isolates. Virion secretion requires interaction between core particles and ENVELOPE proteins. In the present study, chimeric constructs between genotype B and genotype C clones were generated to identify the structural basis for differential virion secretion...
March 28, 2017: Viruses
https://www.readbyqxmd.com/read/28333957/immune-response-of-rats-vaccinated-orally-with-various-plant-expressed-recombinant-cysteine-proteinase-constructs-when-challenged-with-fasciola-hepatica-metacercariae
#16
Malgorzata Kesik-Brodacka, Agnieszka Lipiec, Monika Kozak Ljunggren, Luiza Jedlina, Katarzyna Miedzinska, Magdalena Mikolajczak, Andrzej Plucienniczak, Andrzej B Legocki, Halina Wedrychowicz
BACKGROUND: Cysteine proteinases of Fasciola hepatica are important candidates for vaccine antigens because of their role in fluke biology and host-parasite relationships. In our previous experiments, we found that a recombinant cysteine proteinase cloned from adult F. hepatica (CPFhW) can protect rats against liver fluke infections when it is administered intramuscularly or intranasally in the form of cDNA. We also observed considerable protection upon challenge following mucosal vaccination with inclusion bodies containing recombinant CPFhW produced in Escherichia coli...
March 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28260621/differential-regulation-of-hepatitis-b-virus-core-protein-expression-and-genome-replication-by-a-small-upstream-open-reading-frame-and-naturally-occurring-mutations-in-the-precore-region
#17
Li Zong, Yanli Qin, Haodi Jia, Lei Ye, Yongxiang Wang, Jiming Zhang, Jack R Wands, Shuping Tong, Jisu Li
Hepatitis B virus (HBV) transcribes two subsets of 3.5-kb RNAs: precore RNA for hepatitis B e antigen (HBeAg) expression, and pregenomic RNA for core and P protein translation as well as genome replication. HBeAg expression could be prevented by mutations in the precore region, while an upstream open reading frame (uORF) has been proposed as a negative regulator of core protein translation. We employed replication competent HBV DNA constructs and transient transfection experiments in Huh7 cells to verify the uORF effect and to explore the alternative function of precore RNA...
May 2017: Virology
https://www.readbyqxmd.com/read/28236308/prmt5-restricts-hepatitis-b-virus-replication-via-epigenetic-repression-of-cccdna-transcription-and-interference-with-pgrna-encapsidation
#18
Wen Zhang, Jieliang Chen, Min Wu, Xiaonan Zhang, Min Zhang, Lei Yue, Yaming Li, Jiangxia Liu, Baocun Li, Fang Shen, Yang Wang, Lu Bai, Ulrike Protzer, Massimo Levrero, Zhenghong Yuan
Chronic hepatitis B virus (HBV) infection remains a major health problem worldwide. The covalently closed circular DNA (cccDNA) minichromosome, which serves as the template for the transcription of viral RNAs, plays a key role in viral persistence. While accumulating evidence suggests that cccDNA transcription is regulated by epigenetic machinery, particularly the acetylation of cccDNA-bound histone 3 (H3) and H4, the potential contributions of histone methylation and related host factors remain obscured. Here, by screening a series of methyltransferases and demethylases, we identified protein arginine methyltransferase 5 (PRMT5) as an effective restrictor of HBV transcription and replication...
February 25, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28228589/capsid-phosphorylation-state-and-hepadnavirus-virion-secretion
#19
Xiaojun Ning, Suresh H Basagoudanavar, Kuancheng Liu, Laurie Luckenbaugh, Duoqian Wei, Chunyan Wang, Bo Wei, Yingren Zhao, Taotao Yan, William Delaney, Jianming Hu
The C-terminal domain (CTD) of hepadnavirus core protein is involved in multiple steps of viral replication. In particular, the CTD is initially phosphorylated at multiple sites to facilitate viral RNA packaging into immature nucleocapsids (NCs) and the early stage of viral DNA synthesis. For the avian hepadnavirus duck hepatitis B virus (DHBV), CTD is dephosphorylated subsequently to facilitate the late stage of viral DNA synthesis and to stabilize NCs containing mature viral DNA. The role of CTD phosphorylation in virion secretion, if any, has remained unclear...
May 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28214886/adenovirus-vector-harboring-the-hbcag-and-tripeptidyl-peptidase-ii-genes-induces-potent-cellular-immune-responses-in-vivo
#20
Quanhui Tan, Siyuan Ma, Jianjun Hu, Xiaohua Chen, Yongsheng Yu, Zhenghao Tang, Guoqin Zang
BACKGROUND: Chronic hepatitis B virus (HBV) infection is associated with a weak but specific cellular immune response of the host to HBV. Tripeptidyl peptidaseⅡ (TPPⅡ), an intracellular macromolecule and proteolytic enzyme, plays an important complementary and compensatory role for the proteasome during viral protein degradation and major histocompatibility complex class I antigen presentation by inducing a specific cellular immune response in vivo. Based on a previous study, we aimed to explore the role of MHC class I antigen presentation in vivo and the mechanisms that may be involved...
2017: Cellular Physiology and Biochemistry
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