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HBV pgRNA

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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/29764511/high-serum-levels-of-pregenomic-rna-reflect-frequently-failing-reverse-transcription-in-hepatitis-b-virus-particles
#2
Kasthuri Prakash, Gustaf E Rydell, Simon B Larsson, Maria Andersson, Gunnar Norkrans, Heléne Norder, Magnus Lindh
BACKGROUND: Hepatocytes infected by hepatitis B virus (HBV) produce different HBV RNA species, including pregenomic RNA (pgRNA), which is reverse transcribed during replication. Particles containing HBV RNA are present in serum of infected individuals, and quantification of this HBV RNA could be clinically useful. METHODS: In a retrospective study of 95 patients with chronic HBV infection, we characterised HBV RNA in serum in terms of concentration, particle association and sequence...
May 15, 2018: Virology Journal
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/29734472/hbv-serum-dna-and-rna-levels-in-nucleos-t-ide-analogue-treated-or-untreated-patients-during-chronic-and-acute-infection
#4
Emily K Butler, Jeffrey Gersch, Anne McNamara, Ka-Cheung Luk, Vera Holzmayer, Maria de Medina, Eugene Schiff, Mary Kuhns, Gavin A Cloherty
Treatment of chronic hepatitis B (CHB) patients with nucleos(t)ide analogues (NA) suppresses HBV DNA synthesis but does not affect synthesis of HBV pregenomic RNA (pgRNA). HBV pgRNA is detectable in the serum during NA treatment and has been proposed as a marker of HBV covalently closed circular DNA (cccDNA) activity within the infected hepatocyte. We developed an automated assay for the quantification of serum HBV pgRNA using a dual-target qRT-PCR approach on the Abbott m2000sp/rt system. We demonstrate accurate detection and quantification of serum HBV RNA...
May 7, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29710475/mir-200c-targets-nuclear-factor-ia-to-suppress-hbv-replication-and-gene-expression-via-repressing-hbv-enhancer-i-activity
#5
Hui Tian, Zhenkun He
BACKGROUND: Hepatitis B virus (HBV) chronic infection is a health problem in the worldwide, with a underlying higher risk of liver cirrhosis and hepaticocellular carcinoma. A number of studies indicate that microRNAs (miRNAs) play vital roles in HBV replication. This study was designed to explore the potential molecular mechanism of miR-200c in HBV replication. METHODS: The expression of miR-200c, nuclear factor IA (NFIA) mRNA, HBV DNA, and HBV RNA (pregenomic RNA (pgRNA), and total RNA) were measured by qRCR...
March 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29669831/hepatitis-b-virus-core-protein-dephosphorylation-occurs-during-pregenomic-rna-encapsidation
#6
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/29602251/tim-3-blockade-promotes-inkt-cell-function-to-inhibit-hbv-replication
#7
Yong Xu, Zehua Wang, Xianhong Du, Yuan Liu, Xiaojia Song, Tixiao Wang, Siyu Tan, Xiaohong Liang, Lifen Gao, Chunhong Ma
Increased expression of T cell immunoglobulin and mucin domain-3 (Tim-3) on invariant natural killer T (iNKT) cells is reported in chronic hepatitis B virus (HBV) infection. However, whether Tim-3 regulates iNKT cells in chronic HBV condition remains unclear. In this study, our results showed that the expression of Tim-3 was up-regulated on hepatic iNKT cells from HBV-transgenic (Tg) mice or iNKT cells stimulated with α-galactosylceramide (α-Galcer). Compared with Tim-3- iNKT cells, Tim-3+ iNKT cells expressed more IFN-γ, IL-4 and CD107a, indicating a strong relationship between Tim-3 and iNKT cell activation...
March 30, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29594956/mechanisms-and-effects-on-hbv-replication-of-the-interaction-between-hbv-core-protein-and-cellular-filamin-b
#8
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/29580980/tumor-suppressor-zhx2-restricts-hepatitis-b-virus-replication-via-epigenetic-and-non-epigenetic-manners
#9
Leiqi Xu, Zhuanchang Wu, Siyu Tan, Zehua Wang, Qinghai Lin, Xiaoyan Li, Xiaojia Song, Yuan Liu, Yang Song, Jie Zhang, Jun Peng, Lifen Gao, Yaoqin Gong, Xiaohong Liang, Xiuli Zuo, Chunhong Ma
Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA), the stable genomic form as the template for viral transcription, plays a crucial role in viral persistence which remains a major global health problem. While accumulating evidence suggests the involvement of transcription factors and epigenetic machinery in cccDNA transcription, the roles of host transcription factors which contribute to epigenetic modification of cccDNA remain largely unknown. Zinc finger and homeoboxes 2 (ZHX2) is abundantly expressed in adult hepatocytes, where it acts as a transcriptional repressor and tumor suppressor by directly inhibiting the promoter activities of target genes...
May 2018: Antiviral Research
https://www.readbyqxmd.com/read/29555628/preclinical-profile-of-ab-423-an-inhibitor-of-hepatitis-b-virus-pgrna-encapsidation
#10
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/29500037/hepatitis-b-virus
#11
Chiaho Shih, Ching-Chun Yang, Gansukh Choijilsuren, Chih-Hsu Chang, An-Ting Liou
This infographic about hepatitis B virus explores its replication cycle, natural history of infection and pathogenesis, and how this can be controlled and treated. Hepatitis B virus (HBV) is a common worldwide blood-borne pathogen. Chronic hepatitis B can progress to an inactive carrier state, and then, in some patients, give rise to cirrhosis and cancer of the liver, leading to death. An HBV surface-antigen vaccine is effective, but treatments are currently not curative. HBV replicates via reverse transcription...
April 2018: Trends in Microbiology
https://www.readbyqxmd.com/read/29491161/relative-abundance-of-integrant-derived-viral-rnas-in-infected-tissues-harvested-from-chronic-hepatitis-b-virus-carriers
#12
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
#13
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/29458131/inhibition-of-hepatitis-b-virus-replication-via-hbv-dna-cleavage-by-cas9-from-staphylococcus-aureus
#14
Yu Liu, Miaoxian Zhao, Mingxing Gong, Ying Xu, Cantao Xie, Haohui Deng, Xueying Li, Hongkai Wu, Zhanhui Wang
Chronic hepatitis B virus (HBV) infection is difficult to cure due to the presence of covalently closed circular DNA (cccDNA). Accumulating evidence indicates that the CRISPR/Cas9 system effectively disrupts HBV genome, including cccDNA, in vitro and in vivo. However, efficient delivery of CRISPR/Cas9 system to the liver or hepatocytes using an adeno-associated virus (AAV) vector remains challenging due to the large size of Cas9 from Streptococcus pyogenes (Sp). The recently identified Cas9 protein from Staphylococcus aureus (Sa) is smaller than SpCas9 and thus is able to be packaged into the AAV vector...
April 2018: Antiviral Research
https://www.readbyqxmd.com/read/29432776/establishment-of-cre-mediated-hbv-recombinant-cccdna-rcccdna-cell-line-for-cccdna-biology-and-antiviral-screening-assays
#15
Min Wu, Jin Li, Lei Yue, Lu Bai, Yaming Li, Jieliang Chen, Xiaonan Zhang, Zhenghong Yuan
Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA), existing in hepatocyte nuclei as a stable minichromosome, plays a central role in the life cycle of the virus and permits the persistence of infection. Despite being essential for HBV infection, little is known about the molecular mechanisms of cccDNA formation, regulation and degradation, and there is no therapeutic agents directly targeting cccDNA, fore mostly due to the lack of robust, reliable and quantifiable HBV cccDNA models. In this study, combined the Cre/loxP and sleeping beauty transposons system, we established HepG2-derived cell lines integrated with 2-60 copies of monomeric HBV genome flanked by loxP sites (HepG2-HBV/loxP)...
April 2018: Antiviral Research
https://www.readbyqxmd.com/read/29288943/design-synthesis-and-evaluation-of-novel-phenyl-propionamide-derivatives-as-non-nucleoside-hepatitis-b-virus-inhibitors
#16
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...
January 20, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29260742/-overexpression-of-dna-methyltransferases-in-persistency-of-cccdna-pool-in-chronic-hepatitis-b
#17
D S Kostyushev, A P Zueva, S A Brezgin, A D Lipatnikov, V N Simirskii, D Glebe, E V Volchkova, G A Shipulin, V P Chulanov
AIM: To define the role of DNA-methyltransferases of type 1 and type 3A in hepatitis B viral cycle. MATERIAL AND METHODS: Human hepatoma cells HepG2 with stable expression of 1.1-mer HBV genome were transfected with vectors encoding DNA-methyltransferase 1 (DNMT1), DNA-methyltransferase 3A (DNMT3A) or were co-transfected with these vectors. Total HBV DNA copy number, relative expression of pregenomic RNA (pgRNA), S-protein-encoding RNA (S-RNA) and cccDNA were analyzed by quantitative and semi-quantitative real-time PCR-analysis with TaqMan probes for assessment of DNMTs-mediated effects on HBV...
2017: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/29214184/protective-effects-of-moringa-oleifera-on-hbv-genotypes-c-and-h-transiently-transfected-huh7-cells
#18
Sina Feustel, Fabiola Ayón-Pérez, Ana Sandoval-Rodriguez, Roberto Rodríguez-Echevarría, Homero Contreras-Salinas, Juan Armendáriz-Borunda, L V Sánchez-Orozco
Chronic hepatitis B infection treatment implicates a long-lasting treatment. M. oleifera extracts contain compounds with antiviral, antioxidant, and antifibrotic properties. In this study, the effect of M. oleifera was evaluated in Huh7 cells expressing either HBV genotypes C or H for the antiviral, antifibrotic, anti-inflammatory, and antioxidative responses. Huh7 cells were treated with an aqueous extract of M. oleifera (leaves) at doses of 0, 30, 45, or 60 μ g/mL. The replicative virus and TGF-β1 , CTGF , CAT , IFN-β1 , and pgRNA expressions were measured by real time...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/29133129/hbsag-mrna-degradation-induced-by-a-dihydroquinolizinone-compound-depends-on-the-hbv-posttranscriptional-regulatory-element
#19
Tianlun Zhou, Timothy Block, Fei Liu, Andrew S Kondratowicz, Liren Sun, Siddhartha Rawat, Jeffrey Branson, Fang Guo, Holly Micolochick Steuer, Hongyan Liang, Lauren Bailey, Chris Moore, Xiaohe Wang, Andy Cuconatti, Min Gao, Amy C H Lee, Troy Harasym, Tim Chiu, Dimitar Gotchev, Bruce Dorsey, Rene Rijnbrand, Michael J Sofia
In pursuit of novel therapeutics targeting the hepatitis B virus (HBV) infection, we evaluated a dihydroquinolizinone compound (DHQ-1) that in the nanomolar range reduced the production of virion and surface protein (HBsAg) in tissue culture. This compound also showed broad HBV genotype coverage, but was inactive against a panel of DNA and RNA viruses of other species. Oral administration of DHQ-1 in the AAV-HBV mouse model resulted in a significant reduction of serum HBsAg as soon as 4 days following the commencement of treatment...
January 2018: Antiviral Research
https://www.readbyqxmd.com/read/28887167/identification-of-slug-and-sox7-as-transcriptional-repressors-binding-to-the-hepatitis-b-virus-core-promoter
#20
Hui Ling Ko, Tze Hau Lam, Huijin Ng, Jiaying Toh, Liang Wei Wang, Ee Chee Ren
BACKGROUND & AIMS: The Hepatitis B Virus (HBV) may gain entry into non-liver cells but does not actively replicate in them. We investigated the possibility that these cells possess mechanisms that block HBV core promoter (HBVCP) transcription, specifically absent in liver cells, which together with other liver-specific mechanisms, such as sodium-taurocholate cotransporting polypeptide-mediated entry, enable liver cells to effectively produce HBV. METHODS: Liver and non-liver cell lines were screened for their capacity to activate the HBVCP and synthesize pre-genomic RNA (pgRNA)...
September 5, 2017: Journal of Hepatology
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