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https://www.readbyqxmd.com/read/28637752/identification-of-intermediate-in-hepatitis-b-virus-ccc-dna-formation-and-sensitive-and-selective-ccc-dna-detection
#1
Jun Luo, Xiuji Cui, Lu Gao, Jianming Hu
The hepatitis B virus (HBV) covalently closed circular (CCC) DNA functions as the only viral template capable of coding for all the viral RNA species and is thus essential to initiate and sustain viral replication. CCC DNA is converted, in a multi-step and ill-understood process, from a relaxed circular (RC) DNA, in which neither of the two DNA strands is covalently closed. To detect putative intermediates during RC to CCC DNA conversion, two 3' exonucleases Exo I and Exo III, in combination were used to degrade all DNA strands with a free 3' end, which would nevertheless preserve closed circular DNA, either single-stranded (SS) or double-stranded (DS)...
June 21, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28635671/rab33b-controls-hepatitis-b-virus-assembly-by-regulating-core-membrane-association-and-nucleocapsid-processing
#2
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/28634402/enhanced-antiviral-and-antifibrotic-effects-of-short-hairpin-rnas-targeting-hbv-and-tgf-%C3%AE-in-hbv-persistent-mice
#3
Lei Ye, Fangming Kan, Tao Yan, Jiaqi Cao, Leiliang Zhang, Zhijian Wu, Wuping Li
The hepatitis B virus (HBV) causes acute and chronic liver infection, which may lead to liver cirrhosis and hepatocellular carcinoma. Current treatments including interferons and nucleotide analogs, have limited therapeutic effects, underscoring the need to identify effective therapeutic options to inhibit HBV replication and prevent complications. Previous animal models mimicking chronic HBV infection do not faithfully reflect disease progression in humans. Here, we used our established HBV-persistent mouse line with liver fibrosis to evaluate the efficacy of novel therapies...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28632964/long-term-follow-up-of-patients-triply-infected-with-hiv-and-hepatitis-b-and-c-viruses-in-a-comprehensive-hospital-in-central-china
#4
Rongrong Yang, Xien Gui, Yong Xiong, Shicheng Gao
The clinical characteristics of patients triply infected with HIV, HBV and HCV are notable. From January 2005 to June 2014, a total of 115 cART-naive HIV/HBV/HCV infected individuals were studied and 91 of them were followed-up consecutively after cART with 3TC. After cART with 3TC, the HBV-DNA positive rate decreased from 37.4% (43/115) to 9.9% (9/91) (P<0.001), whereas the HCV-RNA positive rate increased from 53.9% (62/115) to 70.3% (64/91) (P=0.016), and HCV-RNA level increased from 3.52 log10 copies/ml to 4...
June 20, 2017: Journal of Viral Hepatitis
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
#5
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/28627822/development-of-a-one-step-reverse-transcription-loop-mediated-isothermal-amplification-system-for-a-highly-sensitive-detection-of-rabbit-hepatitis-e-virus
#6
Jing Wang, Hua Zhang, Shengyuan Yan, Yichao Wang, Xin Lu, Hongwei Fu
BACKGROUND: Hepatitis E virus (HEV) is a major cause of acute viral hepatitis in areas with poor sanitation. Rabbit is one of important animal reservoirs of the virus. Reverse transcription-loop-mediated isothermal amplification (RT-LAMP) system is a novel nucleic acid amplification assay, for which the specificity and sensitivity are much higher than that of conventional PCR. However, previously reported RT-LAMP system cannot detect rabbit HEV, which was identified recently and seems to be another potential source of human HEV infection...
May 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/28624194/sustained-inhibition-of-hbv-replication-in%C3%A2-vivo-after-systemic-injection-of-aavs-encoding-artificial-antiviral-primary-micrornas
#7
Mohube Betty Maepa, Abdullah Ely, Wayne Grayson, Patrick Arbuthnot
Chronic infection with hepatitis B virus (HBV) remains a problem of global significance and improving available treatment is important to prevent life-threatening complications arising in persistently infected individuals. HBV is susceptible to silencing by exogenous artificial intermediates of the RNA interference (RNAi) pathway. However, toxicity of Pol III cassettes and short duration of silencing by effectors of the RNAi pathway may limit anti-HBV therapeutic utility. To advance RNAi-based HBV gene silencing, mono- and trimeric artificial primary microRNAs (pri-miRs) derived from pri-miR-31 were placed under control of the liver-specific modified murine transthyretin promoter...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28623307/both-interferon-alpha-and-lambda-can-reduce-all-intrahepatic-hdv-infection-markers-in-hbv-hdv-infected-humanized-mice
#8
Katja Giersch, Maria Homs, Tassilo Volz, Martina Helbig, Lena Allweiss, Ansgar W Lohse, Jörg Petersen, Maria Buti, Teresa Pollicino, Camille Sureau, Maura Dandri, Marc Lütgehetmann
Co-infection with hepatitis B (HBV) and D virus (HDV) is associated with the most severe course of liver disease. Interferon represents the only treatment currently approved. However, knowledge about the impact of interferons on HDV in human hepatocytes is scant. Aim was to assess the effect of pegylated interferon alpha (peg-IFNα) and lambda (peg-IFNλ), compared to the HBV-polymerase inhibitor entecavir (ETV) on all HDV infection markers using human liver chimeric mice and novel HDV strand-specific qRT-PCR and RNA in situ hybridization assays, which enable intrahepatic detection of HDV RNA species...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28614380/interleukin-34-inhibits-hepatitis-b-virus-replication-in-vitro-and-in-vivo
#9
Sheng-Tao Cheng, Hua Tang, Ji-Hua Ren, Xiang Chen, Ai-Long Huang, Juan Chen
BACKGROUND: The hepatitis B virus (HBV) infection could activate the immune system and induce extensive inflammatory response. As the most important inflammatory factor, interleukins are critical for anti-viral immunity. Here we investigated whether interleukin-34 (IL-34) play a role in HBV infection. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we first found that both serum IL-34 and IL-34 mRNA in PBMCs in chronic HBV patients was significantly decreased compared to the healthy controls...
2017: PloS One
https://www.readbyqxmd.com/read/28611341/prevalence-and-molecular-characterization-of-hepatitis-d-virus-in-saudi-arabia-a-single-center-study
#10
Ghazi A Jamjoom, Mai M El-Daly, Esam I Azhar, Hind I Fallatah, Hisham O Akbar, Mohammed Babatin, Abdullah S Alghamdi, Mohammed I Dgdgi, Mohamed A Hamid, Yousef A Qari, Sherif A El-Kafrawy
BACKGROUND/AIMS: Hepatitis D virus (HDV) is a defective RNA virus that is dependent on hepatitis B surface antigen (HBsAg) for transmission and replication. HDV significance arises from the possibility of poor prognosis of hepatitis B virus (HBV) infection. In Saudi Arabia, HDV prevalence varied from 8 to 32% before the HBV vaccination program and ranged from 0 to 14.7% after the vaccination program was started. The last study, performed in 2004, showed a prevalence of 8.6% in hospital-based HBV cases and 3...
May 2017: Saudi Journal of Gastroenterology: Official Journal of the Saudi Gastroenterology Association
https://www.readbyqxmd.com/read/28600137/alternative-splicing-of-hepatitis-b-virus-a-novel-virus-host-interaction-altering-liver-immunity
#11
Marion Duriez, Yassmina Mandouri, Bouchra Lekbaby, Hualin Wang, Aurélie Schnuriger, Francois Redelsperger, Chiara Guerrera, Marine Lefevre, Veronique Fauveau, James Ahodantin, Ivan Quetier, Cerina Chhuon, Samir Gourari, Alexandre Boissonas, Upkar Gill, Patrick Kennedy, Nabil Debzi, Delphine Sitterlin, Mala K Maini, Dina Kremsdorf, Patrick Soussan
BACKGROUND & AIMS: Hepatitis B virus (HBV) RNA can undergo alternative splicing but the relevance of this post-transcriptional regulation remains elusive. Here, the mechanism of HBV alternative splicing regulation and its impact on liver pathogenesis were investigated. METHODS: HBV RNA-interacting proteins were identified by RNA pull-down combined to mass spectrometry analysis. HBV splicing regulation was investigated in chemically and surgically induced liver damage in whole HBV genome transgenic mice and in hepatoma cells...
June 6, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28584639/the-evaluation-of-fibrotic-effects-of-the-hepatitis-b-virus-pre-core-in-hepatic-stellate-cells
#12
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
#13
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
#14
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/28575875/significant-association-of-yap1-and-hspc111-proteins-with-poor-prognosis-in-chinese-gastric-cancer-patients
#15
Shanshan Huang, Lingling Zhu, Yuan Cao, Li Li, Yongtao Xie, Jun Deng, Jianping Xiong
Hippo-YAP1 is a tumor-suppressor signaling pathway that inhibits cell proliferation and accelerates apoptosis. However, the role of YAP1 in gastric cancer (GC) is still in dispute. Ribosomal biogenesis is closely correlated with human malignancies. HBV pre-S2 trans-regulated protein 3 (HSPC111) is a portion of an RNA-dependent complex and plays a crucial role in ribosome biosynthesis. Nevertheless, little is known about the expression and function of this factor in GC. In the present study, we evaluated the significance of YAP1 together with HSPC111 in gastric cancer...
May 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28566379/discovery-and-mechanistic-study-of-benzamide-derivatives-that-modulate-hepatitis-b-virus-capsid-assembly
#16
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/28559272/an-effective-anti-viral-approach-targeting-hepatitis-b-virus-using-njk14047-a-novel-and-selective-biphenyl-amide-p38-mapk-inhibitor
#17
So-Young Kim, Hong Kim, Sang-Won Kim, Na-Rae Lee, Chae-Min Yi, Jinyuk Heo, Bum-Joon Kim, Nam-Jung Kim, Kyung-Soo Inn
Despite recent advances in therapeutic strategies against hepatitis B virus (HBV) infection, chronic hepatitis B still remains as a major global health burden. Recent studies have shown that targeting host factors instead of viral factors can be an effective antiviral strategy with low risk of the development of resistance. Efforts to identify host factors affecting viral replication have identified p38 mitogen-activated protein kinase (MAPK) as a possible target for antiviral strategies against various viruses, including HBV...
May 30, 2017: Antimicrobial Agents and Chemotherapy
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
#18
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/28551625/intrahepatic-hcv-rna-level-and-genotype-1-independently-associate-with-hepatic-reticulon-3-expression
#19
Chih-Lang Lin, Rong-Nan Chien, Kung-Hao Liang, Po-Yuan Ke, Ya-Hui Huang, Chau-Ting Yeh
Background /Aim: Reticulon 3 (RTN3), resides predominantly in the endoplasmic reticulum and has opposite regulatory effects on Hepatitis C virus (HCV) replication through interacting with NS5A and NS4B proteins. This study aimed to unravel the actual effect of RTN3 on HCV replication. MATERIALS AND METHODS: A total of 115 HCV-related hepatocellular carcinoma patients receiving hepatectomy was enrolled in this study. The hepatic HCV RNA and RTN3 protein levels in the non-cancerous liver tissues were examined for clinical analysis...
June 2017: Anticancer Research
https://www.readbyqxmd.com/read/28547581/gender-disparity-in-hepatocellular-carcinoma-hcc-multiple-underlying-mechanisms
#20
REVIEW
Bo Zheng, Yan-Jing Zhu, Hong-Yang Wang, Lei Chen
On the global scale, hepatitis B virus (HBV) infection is the main cause of hepatocellular carcinoma (HCC) especially in regions of Asia where HBV infection is endemic. Epidemiological studies show that the incidence of inflammation-driven HCC in males is three times as high as in females. Recent studies suggest that sex hormones have a crucial role in the pathogenesis and development of HBV-induced HCC. We found that the estrogen/androgen signaling pathway is associated with decreased/increased transcription and replication of HBV genes and can promote the development of HBV infections by up/downregulating HBV RNA transcription and inflammatory cytokines levels, which in turn slow down the progression of HBV-induced HCC...
May 23, 2017: Science China. Life Sciences
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