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HBV core protein

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https://www.readbyqxmd.com/read/29782550/multiple-roles-of-core-protein-linker-in-hepatitis-b-virus-replication
#1
Kuancheng Liu, Laurie Luckenbaugh, Xiaojun Ning, Ji Xi, Jianming Hu
Hepatitis B virus (HBV) core protein (HBc) contains an N-terminal domain (NTD, assembly domain) and a C-terminal domain (CTD), which are linked by a flexible linker region. HBc plays multiple essential roles in viral replication, including capsid assembly, packaging of the viral pregenomic RNA (pgRNA) into nucleocapsids, viral reverse transcription that converts pgRNA to the genomic DNA, and secretion of DNA-containing (complete) virions or genome-free (empty) virions. The HBc linker is generally assumed to act merely as a spacer between NTD and CTD but some results suggest that the linker may affect NTD assembly...
May 21, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29770355/host-regulated-hepatitis-b-virus-capsid-assembly-in-a-mammalian-cell-free-system
#2
Kuancheng Liu, Jianming Hu
The hepatitis B virus (HBV) is an important global human pathogen and represents a major cause of hepatitis, liver cirrhosis and liver cancer. The HBV capsid is composed of multiple copies of a single viral protein, the capsid or core protein (HBc), plays multiple roles in the viral life cycle, and has emerged recently as a major target for developing antiviral therapies against HBV infection. Although several systems have been developed to study HBV capsid assembly, including heterologous overexpression systems like bacteria and insect cells, in vitro assembly using purified protein, and mammalian cell culture systems, the requirement for non-physiological concentrations of HBc and salts and the difficulty in manipulating host regulators of assembly presents major limitations for detailed studies on capsid assembly under physiologically relevant conditions...
April 20, 2018: Bio-protocol
https://www.readbyqxmd.com/read/29760415/rbm24-stabilizes-hepatitis-b-virus-pregenomic-rna-but-inhibits-core-protein-translation-by-targeting-the-terminal-redundancy-sequence
#3
Yongxuan Yao, Bo Yang, Huang Cao, Kaitao Zhao, Yifei Yuan, Yingshan Chen, Zhenhua Zhang, Yun Wang, Rongjuan Pei, Jizheng Chen, Xue Hu, Yuan Zhou, Mengji Lu, Chunchen Wu, Xinwen Chen
The terminal redundancy (TR) sequence of the 3.5-kb hepatitis B virus (HBV) RNA contains sites that govern many crucial functions in the viral life cycle, including polyadenylation, translation, RNA packaging, and DNA synthesis. In the present study, RNA-binding motif protein 24 (RBM24) is shown to be involved in the modulation of HBV replication by targeting the TR of HBV RNA. In HBV-transfected hepatoma cell lines, both knockdown and overexpression of RBM24 led to decreased HBV replication and transcription...
May 14, 2018: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/29753083/level-of-hepatitis-b-hb-core-antibody-associates-with-seroclearance-of-hbv-dna-and-hb-surface-antigen-in-hb-e-antigen-seronegative-patients
#4
Hui-Han Hu, Jessica Liu, Chia-Ling Chang, Chin-Lan Jen, Mei-Hsuan Lee, Sheng-Nan Lu, Li-Yu Wang, Yuan Quan, Ning-Shao Xia, Chien-Jen Chen, Pei-Jer Chen, Hwai-I Yang
BACKGROUND & AIMS: Although a low level of hepatitis B surface antigen (HBsAg) is a marker of hepatitis B virus (HBV) seroclearance, additional biomarkers are needed for more accurate prediction. We investigated whether quantification of antibody against HBV core protein (anti-HBc) can identify patients with undetectable levels of HBV DNA and HBsAg seroclearance among those who were HBV e antigen (HBeAg)-seronegative. METHODS: We performed a retrospective analysis of data from a community-based cohort of individuals (30-65 years old) in Taiwan who were HBsAg seropositive, anti-HCV negative, and free of cirrhosis and or liver cancer, recruited from 1991 through 1992, and evaluated every 6-12 months until June 30, 2004...
May 9, 2018: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29743374/common-and-distinct-capsid-and-surface-protein-requirements-for-secretion-of-complete-and-genome-free-hepatitis-b-virions
#5
Xiaojun Ning, Laurie Luckenbaugh, Kuancheng Liu, Volker Bruss, Camille Sureau, Jianming Hu
During the morphogenesis of hepatitis B virus (HBV), an enveloped virus, two types of virions are secreted: (1) a minor population of complete virions containing a mature nucleocapsid with the characteristic, partially double-stranded, relaxed circular DNA genome and (2) a major population containing an empty capsid with no DNA or RNA (empty virions). Secretion of both types of virions requires interactions between the HBV capsid or core protein (HBc) and the viral surface or envelope proteins. We have studied the requirements from both HBc and envelope proteins for empty virion secretion, in comparison with those for secretion of complete virions...
May 9, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29739114/mutations-in-core-gene-region-of-hepatitis-b-virus-in-patients-with-chronic-hepatitis-b
#6
Sevgi Ciftci, Fahriye Keskin, Neslihan Abaci, Filiz Akyuz, Aris Cakiris, Selim Badur, Sabahattin Kaymakoglu, Duran Ustek
BACKGROUND: The HBV core protein plays a major role in host immune response. Mutations occurring in the HBV core gene may cause alterations in the major epitopes being effective in the host immune response. Until now, the persistent effects of core gene mutations on HBV infections have not been fully understood. The aim of this study is to analyze the core gene mutations for epitopes in the T lymphocytes [T helper (Th) and cytotoxic (CTL)] and B cell and C terminal region in patients with chronic hepatitis using ultra-deep pyrosequencing (UDPS) method...
March 1, 2018: Clinical Laboratory
https://www.readbyqxmd.com/read/29669885/the-heteroaryldihydropyrimidine-bay-38-7690-induces-hepatitis-b-virus-core-protein-aggregates-associated-with-promyelocytic-leukemia-nuclear-bodies-in-infected-cells
#7
Andrew D Huber, Jennifer J Wolf, Dandan Liu, Anna T Gres, Jing Tang, Kelsey N Boschert, Maritza N Puray-Chavez, Dallas L Pineda, Thomas G Laughlin, Emily M Coonrod, Qiongying Yang, Juan Ji, Karen A Kirby, Zhengqiang Wang, Stefan G Sarafianos
Heteroaryldihydropyrimidines (HAPs) are compounds that inhibit hepatitis B virus (HBV) replication by modulating viral capsid assembly. While their biophysical effects on capsid assembly in vitro have been previously studied, the effect of HAP treatment on capsid protein (Cp) in individual HBV-infected cells remains unknown. We report here that the HAP Bay 38-7690 promotes aggregation of recombinant Cp in vitro and causes a time- and dose-dependent decrease of Cp in infected cells, consistent with previously studied HAPs...
April 25, 2018: MSphere
https://www.readbyqxmd.com/read/29669831/hepatitis-b-virus-core-protein-dephosphorylation-occurs-during-pregenomic-rna-encapsidation
#8
Qiong Zhao, Zhanying Hu, Junjun Cheng, Shuo Wu, Yue Luo, Jinhong Chang, Jianming Hu, Ju-Tao Guo
Hepatitis B virus (HBV) core protein consists of N-terminal assembly domain and C-terminal domain (CTD) with seven conserved serines or threonine that are dynamically phosphorylated/dephosphorylated during the viral replication cycle. Sulfamoylbenzaminde derivatives are small molecular core protein allosteric modulators (CpAMs) that bind to the HAP pocket between the core protein dimer-dimer interfaces. CpAM binding alters the kinetics and pathway of capsid assembly and can result in the formation of morphologically "normal" capsids devoid of viral pregenomic (pg) RNA and DNA polymerase...
April 18, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29660648/gold-nanoparticle-decorated-reduced-graphene-oxide-targeting-anti-hepatitis-b-virus-core-antigen
#9
Mohamad Farid Abd Muain, Kooi Hoong Cheo, Muhamad Nadzmi Omar, Amir Syahir Amir Hamzah, Hong Ngee Lim, Abu Bakar Salleh, Wen Siang Tan, Asilah Ahmad Tajudin
Hepatitis B virus core antigen (HBcAg) is the major structural protein of hepatitis B virus (HBV). The presence of anti-HBcAg antibody in a blood serum indicates that a person has been exposed to HBV. This study demonstrated that the immobilization of HBcAg onto the gold nanoparticles-decorated reduced graphene oxide (rGO-en-AuNPs) nanocomposite could be used as an antigen-functionalized surface to sense the presence of anti-HBcAg. The modified rGO-en-AuNPs/HBcAg was then allowed to undergo impedimetric detection of anti-HBcAg with anti-estradiol antibody and bovine serum albumin as the interferences...
April 9, 2018: Bioelectrochemistry
https://www.readbyqxmd.com/read/29594956/mechanisms-and-effects-on-hbv-replication-of-the-interaction-between-hbv-core-protein-and-cellular-filamin-b
#10
Yilin Li, Yishuang Sun, Fuyun Sun, Rong Hua, Chenlin Li, Lang Chen, Deyin Guo, Jingfang Mu
Hepatitis B virus (HBV) infection is one of the major problems that threatens global health. There have been many studies on HBV, but the relationship between HBV and host factors is largely unexplored and more studies are needed to clarify these interactions. Filamin B is an actin-binding protein that acts as a cytoskeleton protein, and it is involved in cell development and several signaling pathways. In this study, we showed that filamin B interacted with HBV core protein, and the interaction promoted HBV replication...
March 28, 2018: Virologica Sinica
https://www.readbyqxmd.com/read/29561254/interleukin-35-stimulates-hepatitis-b-virus-transcription-and-replication-by-targeting-transcription-factor-hnf4%C3%AE
#11
Na-Na Tao, Rui Gong, Xiang Chen, Lin He, Fang Ren, Hai-Bo Yu, Juan Chen, Ji-Hua Ren
Hepatitis B virus (HBV) infection is a major health problem worldwide. Interleukin-35 (IL-35) is a definite immunosuppressive cytokine belonging to the IL-12 family. Nevertheless, the role of IL-35 in HBV replication remains elusive. In this study, we found that the level of HBV DNA replicative intermediates detected by qPCR and Southern blotting analysis was significantly increased by rhIL-35 in a dose-dependent manner. Moreover, HBV 3.5 kb mRNA levels were up-regulated by rhIL-35. The HBV core protein level as well as the HBsAg and HBeAg secretion levels were also increased by rhIL-35...
March 21, 2018: Journal of General Virology
https://www.readbyqxmd.com/read/29555628/preclinical-profile-of-ab-423-an-inhibitor-of-hepatitis-b-virus-pgrna-encapsidation
#12
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/29542854/localizing-conformational-hinges-by-nmr-where-do-hepatitis-b-virus-core-proteins-adapt-for-capsid-assembly
#13
Lauriane Lecoq, Shishan Wang, Thomas Wiegand, Stéphane Bressanelli, Michael Nassal, Beat H Meier, Anja Böckmann
The hepatitis B virus (HBV) icosahedral nucleocapsid is assembled from 240 chemically identical core protein molecules and, structurally, comprises four groups of symmetrically nonequivalent subunits. We show here that this asymmetry is reflected in solid-state NMR spectra of the capsids, in which peak splitting is observed for a subset of residues. We compare this information to dihedral angle variations from available 3D structures and also to computational predictions of "dynamic" domains and molecular hinges...
March 15, 2018: Chemphyschem: a European Journal of Chemical Physics and Physical Chemistry
https://www.readbyqxmd.com/read/29510155/nasal-route-favors-the-induction-of-cd4-t-cell-responses-in-the-liver-of-hbv-carrier-mice-immunized-with-a-recombinant-hepatitis-b-surface-and-core-based-therapeutic-vaccine
#14
Maryline Bourgine, Sandrine Crabe, Yadira Lobaina, Gerardo Guillen, Julio Cesar Aguilar, Marie-Louise Michel
Immunization routes and number of doses remain largely unexplored in therapeutic vaccination. The aim of the present work is to evaluate their impact on immune responses in naïve and hepatitis B virus (HBV)-carrier mouse models following immunization with a non-adjuvanted recombinant vaccine comprising the hepatitis B surface (HBsAg) and core (HBcAg) antigens. Mice were immunized either by intranasal (i.n.), subcutaneous (s.c.) or simultaneous (i.n. + s.c.) routes. Humoral immunity was detected in all the animal models with the induction of a potent antibody (Ab) response against HBcAg, which was stronger than the anti-HBs response...
May 2018: Antiviral Research
https://www.readbyqxmd.com/read/29491161/relative-abundance-of-integrant-derived-viral-rnas-in-infected-tissues-harvested-from-chronic-hepatitis-b-virus-carriers
#15
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
#16
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/29472690/cisplatin-enhances-hepatitis-b-virus-replication-and-pgc-1%C3%AE-expression-through-endoplasmic-reticulum-stress
#17
Xiaosong Li, E Pan, Junke Zhu, Lei Xu, Xuemei Chen, Jingjing Li, Li Liang, Yuan Hu, Jie Xia, Juan Chen, Wannan Chen, Jieli Hu, Kai Wang, Ni Tang, Ailong Huang
Chronic hepatitis B infection remains a serious public health issue worldwide. Hepatitis B virus (HBV) reactivation is commonly reported in patients receiving anticancer therapy, immunosuppressive therapy, or organ and tissue transplantation. However, the precise mechanisms underlying chemotherapeutic agent-related HBV reactivation remain unclear. Here, we report that peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) plays a central role in cisplatin-induced HBV transcription and replication...
February 22, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29447911/fluorescent-protein-tagged-hepatitis-b-virus-capsid-protein-with-long-glycine-serine-linker-that-supports-nucleocapsid-formation
#18
Jiang-Yan Chen, Chun-Yang Gan, Xue-Fei Cai, Wen-Lu Zhang, Quan-Xin Long, Xia-Fei Wei, Yuan Hu, Ni Tang, Juan Chen, Haitao Guo, Ai-Long Huang, Jie-Li Hu
Fusion core proteins of Hepatitis B virus can be used to study core protein functions or capsid trafficking. A problem in constructing fusion core proteins is functional impairment of the individual domains in these fusion proteins, might due to structural interference. We reported a method to construct fusion proteins of Hepatitis B virus core protein (HBc) in which the functions of fused domains were partially kept. This method follows two principles: (1) fuse heterogeneous proteins at the N terminus of HBc; (2) use long Glycine-serine linkers between the two domains...
May 2018: Journal of Virological Methods
https://www.readbyqxmd.com/read/29401603/hepatitis-b-virus-core-protein-promotes-hepatocarcinogenesis-by-enhancing-src-expression-and-activating-the-src-pi3k-akt-pathway
#19
Wei Liu, Teng-Fei Guo, Zhen-Tang Jing, Zhi Yang, Lei Liu, Yuan-Ping Yang, Xu Lin, Qiao-Yun Tong
Hepatitis B virus core protein (HBc) is expressed preferentially in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). HBc can function as an oncogene arising from its gene regulatory properties, but how it contributes functionally to hepatocarcinogenesis remains unclear. In this study, we determined the molecular and functional roles of HBc during HBV-associated hepatocellular tumorigenesis. HBc increased tumor formation of hepatoma cells. Moreover, expression of HBc specifically promoted proliferation of hepatoma cells in vitro...
January 17, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29377794/hepatitis-b-virus-core-protein-allosteric-modulators-can-distort-and-disrupt-intact-capsids
#20
Christopher John Schlicksup, Joseph Che-Yen Wang, Samson Francis, Balasubramanian Venkatakrishnan, William W Turner, Michael VanNieuwenhze, Adam Zlotnick
Defining mechanisms of direct-acting antivirals facilitates drug development and our understanding of virus function. Heteroaryldihydropyrimidines (HAPs) inappropriately activate assembly of hepatitis B virus (HBV) core protein (Cp), suppressing formation of virions. We examined a fluorophore-labeled HAP, HAP-TAMRA. HAP-TAMRA induced Cp assembly and also bound pre-assembled capsids. Kinetic and spectroscopic studies imply that HAP-binding sites are usually not available but are bound cooperatively. Using cryo-EM, we observed that HAP-TAMRA asymmetrically deformed capsids, creating a heterogeneous array of sharp angles, flat regions, and outright breaks...
January 29, 2018: ELife
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