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https://www.readbyqxmd.com/read/29216213/a-multi-scale-spatial-model-of-hepatitis-b-viral-dynamics
#1
Quentin Cangelosi, Shawn A Means, Harvey Ho
Chronic hepatitis B viral infection (HBV) afflicts around 250 million individuals globally and few options for treatment exist. Once infected, the virus entrenches itself in the liver with a notoriously resilient colonisation of viral DNA (covalently-closed circular DNA, cccDNA). The majority of infections are cleared, yet we do not understand why 5% of adult immune responses fail leading to the chronic state with its collateral morbid effects such as cirrhosis and eventual hepatic carcinoma. The liver environment exhibits particularly complex spatial structures for metabolic processing and corresponding distributions of nutrients and transporters that may influence successful HBV entrenchment...
2017: PloS One
https://www.readbyqxmd.com/read/29205714/genetic-variants-in-ntcp-exon-gene-are-associated-with-hbv-infection-status-in-a-chinese-han-population
#2
Wennan Wu, Yongbin Zeng, Jinpiao Lin, Yingying Wu, Tianbin Chen, Zhen Xun, Qishui Ou
OBJECTIVE: Sodium taurocholate co-transporting polypeptide (NTCP) plays an important role in the enterohepatic circulation of bile acids. Recently, NTCP was identified as a hepatitis B virus (HBV) receptor. The aim of this study is to investigate the association of NTCP polymorphisms with HBV clinical outcomes and investigate the relationship between NTCP polymorphisms and the serum bile acid level in Chinese Han population. METHODS: The single nucleotide polymorphisms (SNPs), rs2296651 and rs4646285, were genotyped in 1619 Chinese Han individuals...
December 4, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/29192196/a-robust-cell-culture-system-supporting-the-complete-life-cycle-of-hepatitis-b-virus
#3
Eleftherios Michailidis, Jonathan Pabon, Kuanhui Xiang, Paul Park, Vyas Ramanan, Hans-Heinrich Hoffmann, William M Schneider, Sangeeta N Bhatia, Ype P de Jong, Amir Shlomai, Charles M Rice
The discovery of sodium taurocholate cotransporting polypeptide (NTCP) as the hepatitis B virus (HBV) receptor enabled researchers to create hepatoma cell lines susceptible to HBV infection. Infection in current systems, however, is inefficient and virus fails to spread. Infection efficiency is enhanced by treating cells with polyethylene glycol 8000 (PEG) during infection. However, this alone does not promote virus spread. Here we show that maintaining PEG in culture medium increases the rate of infection by at least one order of magnitude, and, most importantly, promotes virus spread...
November 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29127322/reduced-hepatitis-b-and-d-viral-entry-using-clinically-applied-drugs-as-novel-inhibitors-of-the-bile-acid-transporter-ntcp
#4
Joanne M Donkers, Benno Zehnder, Gerard J P van Westen, Mark J Kwakkenbos, Adriaan P IJzerman, Ronald P J Oude Elferink, Ulrich Beuers, Stephan Urban, Stan F J van de Graaf
The sodium taurocholate co-transporting polypeptide (NTCP, SLC10A1) is the main hepatic transporter of conjugated bile acids, and the entry receptor for hepatitis B virus (HBV) and hepatitis delta virus (HDV). Myrcludex B, a synthetic peptide mimicking the NTCP-binding domain of HBV, effectively blocks HBV and HDV infection. In addition, Myrcludex B inhibits NTCP-mediated bile acid uptake, suggesting that also other NTCP inhibitors could potentially be a novel treatment of HBV/HDV infection. This study aims to identify clinically-applied compounds intervening with NTCP-mediated bile acid transport and HBV/HDV infection...
November 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29116221/establishment-of-a-fluorescent-in-situ-hybridization-assay-for-imaging-hepatitis-b-virus-nucleic-acids-in-cell-culture-models
#5
Xiaonan Zhang, Lei Yue, Zhanqing Zhang, Zhenghong Yuan
While chronic hepatitis B remains a global public health problem, the detailed spatiotemporal dynamics of the key molecular events leading to the multiplication and egress of hepatitis B virus (HBV) are still largely unclear. Previously, we developed a chromogenic in situ hybridization assay for detection of HBV RNA, DNA and covalently closed circular DNA in clinical liver biopsies. Here, we report the establishment of a fluorescent in situ hybridization method for the visualization of HBV RNA, HBV core particle DNA and intranuclear DNA in a tetracycline-inducible HBV replication system (HepAD38) and a de novo infection system (HepG2-NTCP)...
November 8, 2017: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/29089529/heparin-at-physiological-concentration-can-enhance-peg-free-in-vitro-infection-with-human-hepatitis-b-virus
#6
Gansukh Choijilsuren, Ren-Shiang Jhou, Shu-Fan Chou, Ching-Jen Chang, Hwai-I Yang, Yang-Yuan Chen, Wan-Long Chuang, Ming-Lung Yu, Chiaho Shih
Hepatitis B virus (HBV) is a blood-borne pathogen responsible for chronic hepatitis, cirrhosis, and liver cancer. The mechanism of HBV entry into hepatocytes remains to be investigated. Recently, sodium taurocholate cotransporting polypeptide (NTCP) was discovered as a major HBV receptor based on an in vitro infection system using NTCP-reconstituted HepG2 cells. However, this infection system relies on the compound polyethylene glycol (4% PEG), which is not physiologically relevant to human infection. High concentration of heparin has been commonly used as an inhibitor control for in vitro infection in the field...
October 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29059468/hepatitis-b-virus-sensitivity-to-interferon-%C3%AE-in-hepatocytes-is-more-associated-with-cellular-interferon-response-than-with-viral-genotype
#7
Fang Shen, Yaming Li, Yang Wang, Vitina Sozzi, Peter A Revill, Jiangxia Liu, Lu Gao, Guang Yang, Mengji Lu, Kathrin Sutter, Ulf Dittmer, Jieliang Chen, Zhenghong Yuan
Interferon-α (IFN-α) is used to treat chronic HBV infection but only 20-40% of patients respond well. Clinical observations have suggested that HBV genotype is associated with the response to IFN therapy, however, its role in viral responsiveness to IFN in HBV-infected hepatocytes remain unclear. Here, we produced infectious virions of HBV genotypes A to D to infect three well-recognized cell culture-based HBV infection systems including primary human hepatocytes (PHH), differentiated HepaRG (dHepaRG) and HepG2-NTCP cells to quantitatively compare the antiviral effect of IFN-α on HBV across genotypes and cell models...
October 23, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28962642/upregulation-of-sodium-taurocholate-cotransporter-polypeptide-during-hepatogenic-differentiation-of-umbilical-cord-matrix-mesenchymal-stem-cells-facilitates-hepatitis-b-entry
#8
Camillo Sargiacomo, Hoda El-Kehdy, Kai Dallmeier, Joery de Kock, Clara Hernandez-Kelly, Vera Rogiers, Arturo Ortega, Johan Neyts, Etienne Sokal, Mustapha Najimi
BACKGROUND: Hepatitis B virus (HBV) carriers worldwide number approximately 240 million people and around 780,000 people die every year from HBV infection. HBV entry and uptake are functionally linked to the presence of the human sodium-taurocholate cotransporting peptide (hNTCP) receptor. Recently, our group demonstrated that human umbilical cord matrix stem cells (UCMSCs) become susceptible to HBV after in-vitro hepatogenic differentiation (D-UCMSCs). METHODS: In the present study, we examined the involvement of hNTCP in governing D-UCMSC susceptibility to HBV infection by characterizing the modulation of this transporter expression during hepatogenic differentiation and by appreciating the inhibition of its activity on infection efficacy...
September 29, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28958921/ifna2-p-ala120thr-impairs-the-inhibitory-activity-of-interferon-%C3%AE-2-against-the-hepatitis-b-virus-through-altering-its-binding-to-the-receptor
#9
Chuming Chen, Xiang Zhu, Wenxiong Xu, Fangji Yang, Genglin Zhang, Lina Wu, Yongyuan Zheng, Zhiliang Gao, Chan Xie, Liang Peng
BACKGROUND: Our previous study found that a rare genetic mutation IFNA2p.Ala120Thr affects the structure of IFN-α2 and contributes to increased host susceptibility to CHB. However, the way in which the single amino acid residue mutation affects IFN-α2 activity is unclear. The purpose of this research was to investigate the effects and mechanisms of IFNA2p.Ala120Thr on IFN-α2 activity. METHODS: Plasmid transfection of BL-21 was used to construct both wild type IFNA2 (wt) and p...
September 25, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28949917/a-potent-human-neutralizing-antibody-fc-dependently-reduces-established-hbv-infections
#10
Dan Li, Wenhui He, Ximing Liu, Sanduo Zheng, Yonghe Qi, Huiyu Li, Fengfeng Mao, Juan Liu, Yinyan Sun, Lijing Pan, Kaixin Du, Keqiong Ye, Wenhui Li, Jianhua Sui
Hepatitis B virus (HBV) infection is a major global health problem. Currently-available therapies are ineffective in curing chronic HBV infection. HBV and its satellite hepatitis D virus (HDV) infect hepatocytes via binding of the preS1 domain of its large envelope protein to sodium taurocholate cotransporting polypeptide (NTCP). Here, we developed novel human monoclonal antibodies that block the engagement of preS1 with NTCP and neutralize HBV and HDV with high potency. One antibody, 2H5-A14, functions at picomolar level and exhibited neutralization-activity-mediated prophylactic effects...
September 26, 2017: ELife
https://www.readbyqxmd.com/read/28915572/down-regulation-of-ntcp-expression-by-cyclin-d1-in-hepatitis-b-virus-related-hepatocellular-carcinoma-has-clinical-significance
#11
Jingting Kang, Jie Wang, Jin Cheng, Zhiliang Cao, Ran Chen, Huiyu Li, Shuang Liu, Xiangmei Chen, Jianhua Sui, Fengmin Lu
The sodium-dependent taurocholate cotransporter polypeptide (NTCP) has been identified as a liver specific functional receptor for the hepatitis B virus (HBV). Previous studies indicated that the expression of NTCP may be associated with the proliferation status of hepatocytes. However, the involvement of NTCP in hepatocellular carcinoma (HCC) cells proliferation remains unclear. In this study, we confirmed that NTCP was down-regulated in HCC tumor tissues compared with that in the adjacent non-tumor tissues (P < 0...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28887167/identification-of-slug-and-sox7-as-transcriptional-repressors-binding-to-the-hepatitis-b-virus-core-promoter
#12
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
https://www.readbyqxmd.com/read/28802063/hepatitis-b-virus-pregenomic-rna-in-hepatocellular-carcinoma-a-nosological-and-prognostic-determinant
#13
Boris Halgand, Christophe Desterke, Lise Rivière, Guillaume Fallot, Mylène Sebagh, Julien Calderaro, Paulette Bioulac-Sage, Christine Neuveut, Marie-Annick Buendia, Didier Samuel, Cyrille Féray
Hepatitis B virus (HBV) is a major cause of hepatocellular carcinoma (HCC). However, very little is known about the replication of HBV in HCC tissues. PATIENTS AND METHODS: We analysed viral and cellular parameters in HCC (T) and non-tumor liver (NT) samples from 99 HBsAg-positive, virologically suppressed patients treated by tumour resection or liver transplantation. We examined total HBV DNA and RNA as well as covalently closed circular DNA (cccDNA) and pregenomic RNA (pgRNA), which are considered as markers of active HBV replication...
August 12, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28717041/activation-of-stimulator-of-interferon-genes-in-hepatocytes-suppresses-the-replication-of-hepatitis-b-virus
#14
Fang Guo, Liudi Tang, Sainan Shu, Mohit Sehgal, Muhammad Sheraz, Bowei Liu, Qiong Zhao, Junjun Cheng, Xuesen Zhao, Tianlun Zhou, Jinhong Chang, Ju-Tao Guo
Induction of interferon and proinflammatory cytokines is a hallmark of the infection of many different viruses. However, hepatitis B virus (HBV) does not elicit a detectable cytokine response in infected hepatocytes. In order to investigate the molecular mechanism underlying the innate immune evasion, a functional cyclic GMP-AMP (cGAMP) synthase (cGAS)-stimulator of interferon genes (STING) pathway was reconstituted in a human hepatoma cell line supporting tetracycline-inducible HBV replication. It was demonstrated that induction of HBV replication neither activated nor inhibited this cytosolic DNA sensing pathway...
October 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28709658/ngago-gdna-system-efficiently-suppresses-hepatitis-b-virus-replication-through-accelerating-decay-of-pregenomic-rna
#15
Zhuanchang Wu, Siyu Tan, Leiqi Xu, Lifen Gao, Haizhen Zhu, Chunhong Ma, Xiaohong Liang
Covalently closed circular DNA (cccDNA) in the hepatocytes nucleus is responsible for persistent infection of Hepatitis B virus (HBV). Current antiviral therapy drugs nucleos(t)ide analogs or interferon fail to eradicate HBV cccDNA. Genome editing technique provides an effective approach for HBV treatment through targeting viral cccDNA. Natronobacterium gregoryi Argonaute (NgAgo)-guide DNA (gDNA) system with powerful genome editing prompts us to explore its application in inhibiting HBV replication. Preliminary function verification indicated that NgAgo/EGFP-gDNA obviously inhibited EGFP expression...
July 12, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28635613/association-of-the-s267f-variant-on-ntcp-gene-and-treatment-response-to-pegylated-interferon-in-patients-with-chronic-hepatitis-b-a-multicentre-study
#16
Kessarin Thanapirom, Sirinporn Suksawatamnuay, Wattana Sukeepaisarnjaroen, Sombat Treeprasertsuk, Tawesak Tanwandee, Phunchai Charatcharoenwitthaya, Satawat Thongsawat, Apinya Leerapun, Teerha Piratvisuth, Rattana Boonsirichan, Chalermrat Bunchorntavakul, Chaowalit Pattanasirigool, Bubpha Pornthisarn, Supoj Tuntipanichteerakul, Ekawee Sripariwuth, Woramon Jeamsripong, Teeranan Sanpanjit, Yong Poovorawan, Piyawat Komolmit
BACKGROUND: Sodium taurocholate co-transporting polypeptide (NTCP) is a cell receptor for hepatitis B virus (HBV). The S267F variant on the NTCP gene is inversely associated with the chronicity of HBV infection, progression to cirrhosis and hepatocellular carcinoma in East Asian populations. This aim of this study was to determine whether the S267F variant was associated with response to pegylated interferon (Peg-IFN) in patients with chronic HBV infection. METHODS: Two hundred and fifty-seven patients with chronic HBV, treated with Peg-IFN for 48 weeks, were identified from 13 tertiary hospitals included in the hepatitis B database of the Thai Association for the Study of the Liver (THASL)...
June 21, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28624460/identification-of-kx2-391-as-an-inhibitor-of-hbv-transcription-by-a-recombinant-hbv-based-screening-assay
#17
Keisuke Harada, Hironori Nishitsuji, Saneyuki Ujino, Kunitada Shimotohno
Antiviral therapies for chronic hepatitis B virus (HBV) infection that are currently applicable for clinical use are limited to nucleos(t)ide analogs targeting HBV polymerase activity and pegylated interferon alpha (PEG-IFN). Towards establishing an effective therapy for HBV related diseases, it is important to develop a new anti-HBV agent that suppresses and eradicates HBV. This study used recombinant HBV encoding NanoLuc to screen anti-HBV compounds from 1827 US Food and Drug Administration approved compounds and identified several compounds that suppressed HBV infection...
August 2017: Antiviral Research
https://www.readbyqxmd.com/read/28605637/hepatitis-b-surface-antigen-on-subviral-particles-reduces-the-neutralizing-effect-of-anti-hbs-antibodies-on-hepatitis-b-viral-particles-in-vitro
#18
Gustaf E Rydell, Kasthuri Prakash, Heléne Norder, Magnus Lindh
During hepatitis B virus (HBV) infections subviral particles (SVP) consisting mainly of hepatitis B surface antigen are present at much higher concentration than viral particles (VP) in serum. To investigate reasons for this excess of SVP production, SVP and VP were fractionated on a Nycodenz gradient and analyzed for HBV infection of HepG2-NTCP cells with and without anti-HBs antibodies. Our findings showed that SVP significantly reduced the neutralization of VP by anti-HBs, while SVP had little effect on viral entry, supporting the assumption that SVP serve as decoy facilitating cell-to-cell spread of HBV in the presence of neutralizing antibodies...
September 2017: Virology
https://www.readbyqxmd.com/read/28429786/comprehensive-assessment-showed-no-associations-of-variants-at-the-slc10a1-locus-with-susceptibility-to-persistent-hbv-infection-among-southern-chinese
#19
Ying Zhang, Yuanfeng Li, Miantao Wu, Pengbo Cao, Xiaomin Liu, Qian Ren, Yun Zhai, Bobo Xie, Yanling Hu, Zhibin Hu, Jinxin Bei, Jie Ping, Xinyi Liu, Yinghua Yu, Bingqian Guo, Hui Lu, Guanjun Liu, Haitao Zhang, Ying Cui, Zengnan Mo, Hongbing Shen, Yi-Xin Zeng, Fuchu He, Hongxing Zhang, Gangqiao Zhou
The sodium taurocholate cotransporting polypeptide (NTCP) encoded by SLC10A1 was recently demonstrated to be a functional receptor for hepatitis B virus (HBV). The role of SLC10A1 polymorphisms, particularly the Ser267Phe variant (rs2296651) in exon 4, has been frequently investigated in regard to risk of persistent HBV infection. However, these investigations have generated conflicting results. To examine whether common genetic variation at the SLC10A1 locus is associated with risk of persistent HBV infection, haplotype-tagging and imputed single nucleotide polymorphisms (SNPs) were assessed in two case-control sample sets, totally including 2,550 cases (persistently HBV infected subjects, PIs) and 2,124 controls (spontaneously recovered subjects, SRs) of Southern Chinese ancestry...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28387980/immune-balance-in-hepatitis-b-infection-present-and-future-therapies
#20
REVIEW
A K Vyas, A Jindal, S Hissar, G Ramakrishna, N Trehanpati
Chronic hepatitis B virus (HBV) infection affects millions of people worldwide and about half a million people die every year. India represents the second largest pool of chronic HBV infections with an estimated 40 million chronically infected patients. Persistence or clearance of HBV infection mainly depends upon host immune responses. Chronically infected individuals remain in immune tolerant phase unless HBV flares and leads to the development of chronic active hepatitis or acute-on-chronic liver failure...
July 2017: Scandinavian Journal of Immunology
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