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HBV core protein

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https://www.readbyqxmd.com/read/28499864/role-of-hepatitis-b-core-protein-in-hbv-transcription-and-recruitment-of-histone-acetyltransferases-to-cccdna-minichromosome
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/28214858/hepatitis-b-virus-core-antigen-stimulates-il-6-expression-via-p38-erk-and-nf-%C3%AE%C2%BAb-pathways-in-hepatocytes
#13
Zhi Chen, Yang-Xia Li, Hai-Jing Fu, Yan-Li Ren, Ling Zou, Shi-Zhen Shen, Ping Chen, Ting Sun, Chun-Hong Huang
BACKGROUND: Hepatitis B virus (HBV) causes both acute and chronic liver injury. Viral proteins are involved in the pathological progress. Hepatitis B core antigen (HBcAg), a component of viral nucleocapsid, is not only essential for HBV lifecycle, but also exhibits strong immunogenicity. The cytoplasmic location of HBcAg in liver biopsy is associated with liver injury and inflammation, but the exact mechanisms remain to be elaborated. METHODS: Huh7, SMMC-7721 and L-02 cells were transfected with pEGFP-N1-HBcAg to establish an intracellular HBcAg expression model...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28205569/heteroaryldihydropyrimidine-hap-and-sulfamoylbenzamide-sba-inhibit-hepatitis-b-virus-replication-by-different-molecular-mechanisms
#14
Zheng Zhou, Taishan Hu, Xue Zhou, Steffen Wildum, Fernando Garcia-Alcalde, Zhiheng Xu, Daitze Wu, Yi Mao, Xiaojun Tian, Yuan Zhou, Fang Shen, Zhisen Zhang, Guozhi Tang, Isabel Najera, Guang Yang, Hong C Shen, John A T Young, Ning Qin
Heteroaryldihydropyrimidine (HAP) and sulfamoylbenzamide (SBA) are promising non-nucleos(t)ide HBV replication inhibitors. HAPs are known to promote core protein mis-assembly, but the molecular mechanism of abnormal assembly is still elusive. Likewise, the assembly status of core protein induced by SBA remains unknown. Here we show that SBA, unlike HAP, does not promote core protein mis-assembly. Interestingly, two reference compounds HAP_R01 and SBA_R01 bind to the same pocket at the dimer-dimer interface in the crystal structures of core protein Y132A hexamer...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28148795/hepatitis-b-virus-encoded-microrna-controls-viral-replication
#15
Xi Yang, Hongfeng Li, Huahui Sun, Hongxia Fan, Yaqi Hu, Min Liu, Xin Li, Hua Tang
MicroRNAs (miRNAs) are a class of small, single-stranded, noncoding, functional RNAs. Hepatitis B virus (HBV) is an enveloped DNA virus with virions and subviral forms of particles that lack a core. It was not known whether HBV encodes miRNAs. Here, we identified an HBV-encoded miRNA (called HBV-miR-3) by deep sequencing and Northern blotting. HBV-miR-3 is located at nucleotides (nt) 373 to 393 of the HBV genome and was generated from 3.5-kb, 2.4-kb, and 2.1-kb HBV in a classic miRNA biogenesis (Drosha-Dicer-dependent) manner...
May 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28112229/multi-omics-analyses-reveal-metabolic-alterations-regulated-by-hepatitis-b-virus-core-protein-in-hepatocellular-carcinoma-cells
#16
Qi Xie, Fengxu Fan, Wei Wei, Yang Liu, Zhongwei Xu, Linhui Zhai, Yingzi Qi, Bingyu Ye, Yao Zhang, Sumit Basu, Zhihu Zhao, Junzhu Wu, Ping Xu
Chronic hepatitis B virus (HBV) infection is partly responsible for hepatitis, fatty liver disease and hepatocellular carcinoma (HCC). HBV core protein (HBc), encoded by the HBV genome, may play a significant role in HBV life cycle. However, the function of HBc in the occurrence and development of liver disease is still unclear. To investigate the underlying mechanisms, HBc-transfected HCC cells were characterized by multi-omics analyses. Combining proteomics and metabolomics analyses, our results showed that HBc promoted the expression of metabolic enzymes and the secretion of metabolites in HCC cells...
January 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/27978927/-zinc-finger-e-box-binding-homeobox-2-inhibits-hepatitis-b-virus-replication-and-expression
#17
X P Li, Q Hu, Q He, W X Chen
Objective: To investigate the effect of zinc finger E-box-binding homeobox 2 (ZEB2) on hepatitis B virus (HBV) replication and expression. Methods: HepG2, HepG2.2.15, and HepAD38 cells were cultured separately, and Western blot was used to measure the expression of ZEB2. HepG2.2.15 cells were cultured and transfected with ZEB2 expression plasmids or shRNA targeting ZEB2. Western blot was used to measure the expression of ZEB2 and HBV core proteins, quantitative real-time PCR was used to measure HBV 3.5 kb RNA and HBV DNA, Southern blot was used to measure HBV replicative intermediate, and ELISA was used to measure the expression of HBsAg and HBeAg, in order to clarify the effect of ZEB2 on HBV replication and expression...
November 20, 2016: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
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
#18
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/27975307/a-homokaryon-assay-for-nucleocytoplasmic-shuttling-activity-of-hbv-core-protein
#19
Ching-Chun Yang, Hung-Cheng Li, Chiaho Shih
Hepatitis B virus (HBV) core protein (HBc) can be present in both nucleus and cytoplasm. The arginine-rich domain (ARD) at the cytoplasmic tail of HBc contains both a nuclear localization signal (NLS) and nuclear export signal (NES). We established a homokaryon assay to detect the dynamic trafficking of HBc between nucleus and cytoplasm in hepatocytes. Using immunofluorescence assay (IFA) and PEG-induced cell-cell fusion, we demonstrated that a chimeric reporter protein of SV40 large T antigen, when fused in-frame with HBc ARD, can shuttle from a donor nuclei (green) to the recipient nuclei (red) in the context of binucleated or polynucleated hybrid cells...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27958343/hbv-maintains-electrostatic-homeostasis-by-modulating-negative-charges-from-phosphoserine-and-encapsidated-nucleic-acids
#20
Pei-Yi Su, Ching-Jen Yang, Tien-Hua Chu, Chih-Hsu Chang, Chiayn Chiang, Fan-Mei Tang, Chih-Yin Lee, Chiaho Shih
Capsid assembly and stability of hepatitis B virus (HBV) core protein (HBc) particles depend on balanced electrostatic interactions between encapsidated nucleic acids and an arginine-rich domain (ARD) of HBc in the capsid interior. Arginine-deficient ARD mutants preferentially encapsidated spliced viral RNA and shorter DNA, which can be fully or partially rescued by reducing the negative charges from acidic residues or serine phosphorylation of HBc, dose-dependently. Similarly, empty capsids without RNA encapsidation can be generated by ARD hyper-phosphorylation in insect, bacteria, and human hepatocytes...
December 13, 2016: Scientific Reports
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