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HBV core protein

Satadru Jha, Federico Ramadori, Santina Quarta, Alessandra Biasiolo, Enrica Fabris, Paola Baldan, Gaetano Guarino, Mariagrazia Ruvoletto, Gianmarco Villano, Cristian Turato, Angelo Gatta, Fabrizio Mancin, Patrizia Pontisso, Paolo Scrimin
One of the most daunting challenges of nanomedicine is the finding of appropriate targeting agents to deliver suitable payloads precisely to cells affected by malignancies. Even more complex is to achieve the ability to ensure the nanosystems enter those cells. Here we use 2 nm (metal core) gold nanoparticles to target human hepatocellular carcinoma (HepG2) cells stably transfected with the SERPINB3 (SB3) protein. The nanoparticles were coated with a 85:15 mixture of thiols featuring, respectively, a phosphoryl choline, to ensure water solubility and biocompatibility, and a 28-mer peptide corresponding to the amino acid sequence 21-47 of the hepatitis B virus-PreS1 protein (PreS1(21-47))...
October 22, 2016: Bioconjugate Chemistry
Frank Tacke, Daniela C Kroy
Persistent hepatitis B virus (HBV) infections affect about 240 million patients worldwide that are at risk of developing liver cirrhosis or hepatocellular carcinoma. HBV is a small, partially double stranded DNA virus with four overlapping genes and a unique life cycle, which involves the generation of an RNA template for replication via reverse transcription. Mutations occur frequently during chronic infection, and particular selection pressures select distinct mutants. Nucleoside and nucleotide analogues like lamivudine (LMV), entecavir (ETV), telbivudine (LdT), adefovir dipivoxil (ADV) and tenofovir (TDF) are used to achieve long-term suppression of viral replication...
September 2016: Annals of Translational Medicine
Chengliang Zhu, Guosheng Gao, Hui Song, Fengxia Xu, Kailang Wu, Xinghui Liu
BACKGROUND: Hepatitis B virus (HBV) infection causes lipid metabolism disorders. Apolipoprotein A5 (ApoA5) is a new apolipoprotein family member that plays an important role in the regulation of lipid metabolism. The present study was to investigate the impact of HBV on ApoA5 expression and its regulatory mechanism. METHODS: Reverse transcription polymerase chain reaction (RT-PCR) and western blotting were used to measure ApoA5 mRNA and protein expression in HepG2 and HepG2...
October 10, 2016: Lipids in Health and Disease
Bing-Fang Chen
AIM: To investigate the associations of different types of pre-S deletions with hepatitis B virus (HBV) genotypes. METHODS: The sequences of the pre-S region, basal core promoter (BCP) mutation, and precore (PC) mutation were examined through direct DNA sequencing or clonal analysis and sequencing in 273 HBV carriers, namely 55 asymptomatic carriers, 55 carriers with chronic hepatitis (CH), 55 with liver cirrhosis (LC), 53 with liver cirrhotic hepatocellular carcinoma (LC-HCC), and 55 with noncirrhotic HCC...
September 21, 2016: World Journal of Gastroenterology: WJG
P Pumpens, E Grens
This review article is a continuation of the paper "Hepatitis B core particles as a universal display model: a structure-function basis for development" written by Pumpens P. and Grens E., ordered by Professor Lev Kisselev and published in FEBS Letters, 1999, 442, 1-6. The past 17 years have strengthened the paper's finding that the human hepatitis B virus core protein, along with other Hepadnaviridae family member core proteins, is a mysterious, multifunctional protein. The core gene of the Hepadnaviridae genome encodes five partially collinear proteins...
July 2016: Molekuliarnaia Biologiia
Andrew G Cole
The search for a cure for hepatitis B virus infection extends beyond interferon and the existing polymerase inhibitors, and targets different aspects of the virus life cycle to develop agents that operate by alternative mechanisms. Examples of small molecules that disrupt the encapsidation of pgRNA have been known for some time, but recent advances in the understanding of nucleocapsid formation, how compounds interact with core protein, and the development of drug-like molecules have recently progressed the study of capsid assembly modulators to proof of concept in the clinic with respect to reduction of viral load in chronic HBV patients...
September 13, 2016: Current Opinion in Pharmacology
Francisca Sosa-Jurado, Nora Hilda Rosas-Murrieta, Belinda Guzman-Flores, Cintia Perez Zempoaltecalt, Ana Patricia Sanchez Torres, Leticia Ramirez Rosete, Maribel Bernal-Soto, Luis Marquez-Dominguez, Daniel Melendez-Mena, Miguel Angel Mendoza Torres, Maria Teresa Lopez Delgado, Julio Reyes-Leyva, Veronica Vallejo-Ruiz, Gerardo Santos-Lopez
BACKGROUND: The hepatitis B virus (HBV) causes chronic hepatitis, hepatic cirrhosis, and hepatocellular carcinoma. Surface antigen (HBsAg) detection is a definitive test that can confirm HBV infection, while the presence of antibodies against the core protein (anti-HBc) suggests either a previous or ongoing infection or occult hepatitis B infection (OBI). OBJECTIVES: The aim of the present study was to determine the prevalence of anti-HBc and HBsAg in blood donors...
June 2016: Hepatitis Monthly
Chunlan Liu, Dawei Cai, Lin Zhang, Wei Tang, Ran Yan, Haitao Guo, Xulin Chen
The development of new agents to target HBV cccDNA is urgently needed because of the limitations of current available drugs for treatment of hepatitis B. By using a cell-based assay in which the production of HBeAg is in a cccDNA-dependent manner, we screened a compound library derived from Chinese herbal remedies for inhibitors against HBV cccDNA. Three hydrolyzable tannins, specifically punicalagin, punicalin and geraniin, emerged as novel anti-HBV agents. These compounds significantly reduced the production of secreted HBeAg and cccDNA in a dose-dependent manner in our assay, without dramatic alteration of viral DNA replication...
October 2016: Antiviral Research
Chaoyang Chen, Haodi Jia, Fei Zhang, Yanli Qin, Li Zong, Quan Yuan, Yongxiang Wang, Ningshao Xia, Jisu Li, Yumei Wen, Shuping Tong
Hepatitis B virus (HBV) has a 3.2-kb circular DNA genome. It employs four promoters in conjunction with a single polyadenylation signal to generate 3.5-, 2.4-, 2.1-, and 0.7-kb co-terminal RNAs. The 3.5-kb RNA is subdivided into the precore RNA for e antigen expression and pregenomic RNA for genome replication. When introduced to a genotype A clone, several core promoter mutations markedly enhanced HBV genome replication but suppressed e antigen expression through up regulation of pregenomic RNA at the expense of precore RNA...
August 23, 2016: Journal of General Virology
Nimisha Harshadrai Bhoola, Anna Kramvis
BACKGROUND: Hepatitis B virus (HBV) is hyperendemic in southern Africa, with subgenotype A1 prevailing. The precore/core (preC/C) region of A1, encoding for hepatitis B e antigen (HBeAg), has unique sequence characteristics, differentiating it from subgenotypes A2 and D3. Our aim was to follow the expression of HBeAg in vitro by the three subgenotypes. METHODS: Huh7 cells were transfected with plasmids belonging to subgenotypes A1, A2, and D3. Using indirect immunofluorescence, the expression of HBeAg was followed, as was the activation of the unfolded protein response (UPR) and subsequent activation of apoptosis...
2016: Intervirology
Carla Osiowy, Carla Coffin, Anton Andonov
There are only two currently approved classes of hepatitis B virus (HBV) antiviral agents, pegylated interferon (Peg-IFN), and nucleos(t)ide analogs (NAs) for chronic HBV infection. Although Peg-IFN is used for a finite 48-week duration and offers a greater chance of sustained off-treatment virological response, it is poorly tolerated and can only be offered to selected patients. The NAs are well tolerated but require prolonged therapy due to risk of relapse with treatment cessation. There is evolving data that novel virological assays (e...
2016: Current Treatment Options in Infectious Diseases
Chao Chen, Joseph Che-Yen Wang, Elizabeth E Pierson, David Z Keifer, Mildred Delaleau, Lara Gallucci, Christian Cazenave, Michael Kann, Martin F Jarrold, Adam Zlotnick
Hepatitis B virus (HBV) capsids are found in many forms: immature single-stranded RNA-filled cores, single-stranded DNA-filled replication intermediates, mature cores with relaxed circular double-stranded DNA, and empty capsids. A capsid, the protein shell of the core, is a complex of 240 copies of core protein. Mature cores are transported to the nucleus by a complex that includes both importin α and importin β (Impα and Impβ), which bind to the core protein's C-terminal domains (CTDs). Here we have investigated the interactions of HBV core protein with importins in vitro...
August 2016: PLoS Pathogens
Tsutomu Nishizawa, Takashi Hoshino, Atsushi Naganuma, Tominari Kobayashi, Shigeo Nagashima, Masaharu Takahashi, Hitoshi Takagi, Hiroaki Okamoto
The viral factors associated with the development of fulminant hepatitis B are not fully understood. We recently found four unique mutations [G to A at nucleotide 1742 (G1742A), C1766T, T1768A and T1809C] in the basal core promoter (BCP) region of a genotype A hepatitis B virus (HBV) strain (FH) obtained from a 53-year-old man with fatal fulminant hepatitis. To elucidate the association of the mutations of the FH genome with the disease, we constructed a 1.3-fold FH genome and its five variants by replacing one or two mutated nucleotides with wild-type nucleotide(s) via site-directed mutagenesis, and transfected human hepatoma cells (HepG2/C3A) with the constructs...
July 28, 2016: Journal of General Virology
Nuruddin Unchwaniwala, Nathan M Sherer, Daniel D Loeb
UNLABELLED: To understand subcellular sites of hepatitis B virus (HBV) replication, we visualized core (Cp), polymerase (Pol), and pregenomic RNA (pgRNA) in infected cells. Interestingly, we found that the majority of Pol localized to the mitochondria in cells undergoing viral replication. The mitochondrial localization of Pol was independent of both the cell type and other viral components, indicating that Pol contains an intrinsic mitochondrial targeting signal (MTS). Neither Cp nor pgRNA localized to the mitochondria during active replication, suggesting a role other than DNA synthesis for Pol at the mitochondria...
October 1, 2016: Journal of Virology
Gerald Y Minuk, Wendy Bautista, Julianne Klein
Both the hepatitis B virus (HBV) and cancer stem cells (CSCs) have been independently implicated in the pathogenesis of hepatocellular carcinoma (HCC). To date, there have been no reports describing HBV infection within CSCs. In this report we describe HBV core (HBcAg) and HBx protein expression within CSCs associated with human HCC. HBV markers were also identified in nonmalignant stem cells present in adjacent nontumor tissue. These findings provide new insights into the pathogenesis of HBV-induced HCC and are potentially relevant to the treatment of both HCC and chronic HBV...
2016: Canadian Journal of Infectious Diseases & Medical Microbiology
Hong Kim, Seoung-Ae Lee, Bum-Joon Kim
Chronic hepatitis B virus (HBV) infection remains a major health problem, with more than 240 million people chronically infected worldwide and potentially 650000 deaths per year due to advanced liver diseases including liver cirrhosis and hepatocellular carcinoma (HCC). HBV-X protein (HBx) contributes to the biology and pathogenesis of HBV via stimulating virus replication or altering host gene expression related to HCC. The HBV X region contains only 465 bp encoding the 16.5 kDa HBx protein, which also contains several critical cis-elements such as enhancer II, the core promoter and the microRNA-binding region...
June 28, 2016: World Journal of Gastroenterology: WJG
Hao Zhang, Zheng Xing, Saravana Kumar Kailasam Mani, Brigitte Bancel, David Durantel, Fabien Zoulim, Elizabeth J Tran, Philippe Merle, Ourania Andrisani
UNLABELLED: Chronic hepatitis B virus (HBV) infection is a major factor in hepatocellular carcinoma (HCC) pathogenesis by a mechanism not yet understood. Elucidating mechanisms of HBV-mediated hepatocarcinogenesis is needed to gain insights into classification and treatment of HCC. In HBV replicating cells, including virus-associated HCCs, suppressor of zeste 12 homolog (SUZ12), a core subunit of Polycomb repressive complex2 (PRC2), undergoes proteasomal degradation. This process requires the long noncoding RNA, Hox transcript antisense intergenic RNA (HOTAIR)...
October 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Jennifer A Dill, Alvin C Camus, John H Leary, Francesca Di Giallonardo, Edward C Holmes, Terry Fei Fan Ng
UNLABELLED: Hepadnaviruses (hepatitis B viruses [HBVs]) are the only animal viruses that replicate their DNA by reverse transcription of an RNA intermediate. Until recently, the known host range of hepadnaviruses was limited to mammals and birds. We obtained and analyzed the first amphibian HBV genome, as well as several prototype fish HBVs, which allow the first comprehensive comparative genomic analysis of hepadnaviruses from four classes of vertebrates. Bluegill hepadnavirus (BGHBV) was characterized from in-house viral metagenomic sequencing...
September 1, 2016: Journal of Virology
Shinji Takamatsu, Mayuka Shimomura, Yoshihiro Kamada, Haruka Maeda, Tomoaki Sobajima, Hayato Hikita, Masumi Iijima, Yuta Okamoto, Ryo Misaki, Kazuhito Fujiyama, Shushi Nagamori, Yoshikatsu Kanai, Tetsuo Takehara, Keiji Ueda, Shun'ichi Kuroda, Eiji Miyoshi
The functions of cell surface proteins, such as growth factor receptors and virus/bacteria-entry receptors, can be dynamically regulated by oligosaccharide modifications. In the present study, we investigated the involvement of glycosylation in hepatitis B virus (HBV) entry into hepatoma cells. Infection of oligosaccharide-remodeling hepatoma cells with a pseudo virus of HBV, bio-nanocapsule (BNC), was evaluated by flow cytometry and confocal microscopy. Among various experiments using several hepatoma cells, marked difference was observed between Huh6 cells and HB611 cells, which were established by HBV gene transfection into hepatoma cells...
June 21, 2016: Glycobiology
Zhi-Hua Jiang, Qin-Yan Chen, Tim J Harrison, Guo-Jian Li, Xue-Yan Wang, Hai Li, Li-Ping Hu, Kai-Wen Li, Qing-Li Yang, Chao Tan, Zhong-Liao Fang
OBJECTIVES: The aim of this study was to identify serum proteins with differential concentrations between hepatocellular carcinoma (HCC) patients and HBsAg asymptomatic carriers among individuals infected with hepatitis B virus (HBV) with basal core promoter (BCP) double mutations (A1762T, G1764A). METHODS: iTRAQ and liquid chromatography-tandem mass spectrometry were used to identify differentially expressed protein, and an ELISA test was used for the validation test...
2016: Intervirology
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