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HBV core protein

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
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...
March 3, 2018: Antiviral Research
Natalia Freitas, Tetyana Lukash, Sumedha Gunewardena, Benjamin Chappell, Betty L Slagle, Severin O Gudima
Five matching sets of non-malignant liver tissues and HCCs from individuals chronically infected with hepatitis B virus (HBV) were examined. The HBV genomic sequences were determined using overlapping PCR amplicons covering the entire viral genome. Four pairs of tissues were infected with HBV of genotype C, while one pair - with genotype B. HBV replication markers were found in all tissues. In majority of HCC samples, the levels of pre-genomic/pre-core RNA (pgRNA) and covalently closed circular DNA (cccDNA) were lower than those of liver tissue counterparts...
February 28, 2018: Journal of Virology
Smita Nair, Adam Zlotnick
Cytidine deaminases inhibit replication of broad range of DNA viruses by deaminating cytidines on single stranded DNA to generate uracil. While several lines of evidence have revealed 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...
February 28, 2018: Journal of Virology
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
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 Glysine-serine linkers between the two domains...
February 12, 2018: Journal of Virological Methods
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
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
Tatjana Döring, Lisa Zeyen, Christina Bartusch, Reinhild Prange
Previous studies indicated that hepatitis B virus (HBV) stimulates autophagy to favor its production. To understand how HBV co-opts autophagy as a proviral machinery, we studied roles of key autophagy proteins in HBV-replicating liver cell cultures. RNAi-mediated silencing of Atg5, Atg12, and Atg16L1, which promote autophagophore expansion and LC3 membrane conjugation, interfered with viral core/nucleocapsid (NC) formation/stability and strongly diminished virus yields. Concomitantly, core/NC membrane association and their sorting to envelope-positive compartments were perturbed...
January 24, 2018: Journal of Virology
Hyun Wook Seo, Joon Pyung Seo, Yoon Jun Kim, Guhung Jung
Hepatitis B virus (HBV) infection is a major risk factor for chronic liver disease, cirrhosis, and hepatocellular carcinoma (HCC) worldwide. While multiple hepatitis B drugs have been developed, development of drug resistance during treatment or weak efficacies observed in some cases have limited their application. Therefore, there is an urgent need to develop better pharmacological agents for HBV-infected individuals. Here, we identified cetylpyridinium chloride (CPC) as a novel inhibitor of HBV. Using computational analysis of CPC-nucleocapsid proteins, microscale thermophoresis analysis of CPC binding to viral nucleocapsids, and in vitro nucleocapsid formation assays, we found that CPC interacts with dimeric viral nucleocapsid protein (known as core protein or HBcAg)...
January 15, 2018: Biochemical and Biophysical Research Communications
Jenny Wang, Daniel Stenzel, Ally Liu, Dengfeng Liu, Darren Brown, Alexandre Ambrogelly
Therapeutic vaccines represent an emerging class of immune-modulatory treatments for cancer, infections, and chronic diseases. One such vaccine was designed as an immune stimulator of the T cell response against HBV antigens to eliminate HBV infected cells and offer a therapeutic avenue to treat patients suffering from chronic hepatitis B infection. Whole deactivated Saccharomyces cerevisiae cells expressing a recombinant fusion of HBV X, S and Core antigens elicit T cell responses in mice and activate human T cells linked with viral clearance...
January 12, 2018: Analytical Biochemistry
Q Yuan, H You, N S Xia, J D Jia
Hepatitis B core antibody (anti-HBc) targets viral core protein and is produced in patients with hepatitis B virus (HBV) infection, and seroconversion occurs in the early stage of infection and often lasts for a lifetime. Qualitative detection of anti-HBc has been used in clinical practice for many years, while the clinical significance of its quantitative level remains unclear. A novel anti-HBc immunoassay based on double-antigen sandwich ELISA has been developed in recent years and lays a foundation for illustrating the change in the quantitative level of anti-HBc (qAnti-HBc) in HBV infection and its clinical significance...
December 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
H R Hou, Y Kang, Y K Li, Y L Zeng, J F Wei, G G Ding, Z Peng, J Shang
Objective: To investigate the effect of hepatitis B core antigen (HBcAg) in promoting the invasion of hepatitis B virus (HBV)-related hepatocellular carcinoma cell line HepG2.2.15 and the role of Toll-like receptor 4 (TLR4) in the mechanism. Methods: TLR4 mRNA and protein expression in HepG2 cells and HepG2.2.15 cells was measured by reverse transcription real-time PCR and Western blot analysis, respectively. HepG2.2.15 cells were transfected with TLR4 specific small interfering RNA (siRNA) to silence TLR4 expression, and stimulated by recombinant HBcAg in culture...
December 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
Hong Zang, Zhihui Xu, Yan Liu, Xiaodong Li, Yihui Rong, Ling Jiang, Shaoli You, Jinhua Hu, Jun Zhao, Dongping Xu, Shaojie Xin
OBJECTIVE: Mutations occurring within different genes of hepatitis B virus (HBV) genome may have different clinical implications. This study aimed to observe the clinical and virological implications of the A1846T and C1913A/G mutations of HBV genome in the development and treatment outcome of severe liver diseases, which has not been previously determined. MATERIALS AND METHODS: A total of 438 cases of patients with liver diseases were retrospectively reviewed, including 146 with mild chronic hepatitis B infection (CHB-M), 146 with severe chronic hepatitis B infection (CHB-S), and 146 with acute-on-chronic liver failure (ACLF)...
January 11, 2018: Scandinavian Journal of Gastroenterology
Jingying Qiu, Qineng Gong, Jian Gao, Wang Chen, Yinpeng Zhang, Xiaoke Gu, Daoquan Tang
As an ongoing search for potent non-nucleoside anti-HBV agents with novel structures, we described a series of phenyl propionamide derivatives (3a-b, 4a-e, 7a-g, 8a-h and 9a-b) by pharmacophore fusion strategy in the present work. All the compounds exhibited an anti-HBV activity to some extent. Among them, compounds 8d and 9b displayed most potent anti-HBV activity with IC50 values on HBV DNA replication of 0.46 and 0.14 μM, respectively. And the selective index values of 8d and 9b were more than 217.39 and 153...
December 16, 2017: European Journal of Medicinal Chemistry
Makutiro Ghislain Masavuli, Danushka K Wijesundara, Joseph Torresi, Eric J Gowans, Branka Grubor-Bauk
Hepatitis C Virus (HCV) infects 2% of the world's population and is the leading cause of liver disease and liver transplantation. It poses a serious and growing worldwide public health problem that will only be partially addressed with the introduction of new antiviral therapies. However, these treatments will not prevent re-infection particularly in high risk populations. The introduction of a HCV vaccine has been predicted, using simulation models in a high risk population, to have a significant effect on reducing the incidence of HCV...
2017: Frontiers in Microbiology
Ahmed Diab, Adrien Foca, Fabien Zoulim, David Durantel, Ourania Andrisani
Virally encoded proteins have evolved to perform multiple functions, and the core protein (HBc) of the hepatitis B virus (HBV) is a perfect example. While HBc is the structural component of the viral nucleocapsid, additional novel functions for the nucleus-localized HBc have recently been described. These results extend for HBc, beyond its structural role, a regulatory function in the viral life cycle and potentially a role in pathogenesis. In this article, we review the diverse roles of HBc in HBV replication and pathogenesis, emphasizing how the unique structure of this protein is key to its various functions...
January 2018: Antiviral Research
Yaqi Wang, Ting Wu, Danqing Hu, Xinxin Weng, Xiaojing Wang, Pei-Jer Chen, Xiaoping Luo, Hongwu Wang, Qin Ning
Hepatitis B virus (HBV) infection is a prevalent infectious disease with serious outcomes like chronic and acute hepatitis, cirrhosis, and hepatocellular carcinoma. However, the metabolic alteration by HBV is rarely taken into consideration. With the high prevalence of alcohol consumption and chronic HBV infection, their overlap is assumed to be an increasing latent hazard; although the extent has not been calculated. Moreover, the impact of chronic alcohol consumption combined with HBV on cholesterol metabolism is unknown...
January 2018: Journal of Lipid Research
Yanmeng Chen, Jie Hu, Xuefei Cai, Yao Huang, Xing Zhou, Zeng Tu, Jieli Hu, John E Tavis, Ni Tang, Ailong Huang, Yuan Hu
Hepatitis B virus is a partially double-stranded DNA virus that replicates by reverse transcription, which occurs within viral core particles in the cytoplasm. The cytidine deaminase APOBEC3B is a cellular restriction factor for HBV. Recently, it was reported that APOBEC3B can edit HBV cccDNA in the nucleus, causing its degradation. However, whether and how it can edit HBV core-associated DNAs during reverse transcription is unclear. Our studies to address this question revealed the following: First, silencing endogenous APOBEC3B in an HBV infection system lead to upregulation of HBV replication...
January 2018: Antiviral Research
Quentin Osseman, Lara Gallucci, Shelly Au, Christian Cazenave, Elodie Berdance, Marie-Lise Blondot, Aurélia Cassany, Dominique Bégu, Jessica Ragues, Cindy Aknin, Irina Sominskaya, Andris Dishlers, Birgit Rabe, Fenja Anderson, Nelly Panté, Michael Kann
BACKGROUND & AIMS: Hepatitis B virus (HBV) has a DNA genome but replicates within nucleus by transcription of an RNA pregenome, which is converted to DNA in cytoplasmic capsids. Capsids in this compartment are correlated with inflammation and epitopes of the capsid protein core (Cp) are the main target for T cell-mediated immune response. We investigated the mechanism of cytoplasmic capsid transport, which is important for infection but also for cytosolic capsid removal. METHODS: We used virion-derived capsids with a mature rcDNA (matC), empty capsids (empC), and RNA containing capsids (rnaC) as control...
November 4, 2017: Journal of Hepatology
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