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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
#1
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
#2
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
#3
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
#4
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
#5
Hui Ling Ko, Tze Hau Lam, Huijin Ng, Jiaying Toh, Liang Wei Wang, Ee Chee Ren
BACKGROUND & AIMS: The Hepatitis B Virus (HBV) is carried in many non-liver cell types but does not actively replicate in them. We investigated the possibility that these cells possess HBVCP transcription inhibitory mechanisms specifically absent in liver cells, which together with other liver-specific mechanisms such as NTCP-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 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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/28374759/human-induced-pluripotent-stem-cell-derived-hepatocyte-like-cells-as-an-in-vitro-model-of-human-hepatitis-b-virus-infection
#14
Fuminori Sakurai, Seiji Mitani, Tatsuro Yamamoto, Kazuo Takayama, Masashi Tachibana, Koichi Watashi, Takaji Wakita, Sayuki Iijima, Yasuhito Tanaka, Hiroyuki Mizuguchi
In order to understand the life cycle of hepatitis B virus (HBV) and to develop efficient anti-HBV drugs, a useful in vitro cell culture system which allows HBV infection and recapitulates virus-host interactions is essential; however, pre-existing in vitro HBV infection models are often problematic. Here, we examined the potential of human induced-pluripotent stem (iPS) cell-derived hepatocyte-like cells (iPS-HLCs) as an in vitro HBV infection model. Expression levels of several genes involved in HBV infection, including the sodium taurocholate cotransporting polypeptide (NTCP) gene, were gradually elevated as the differentiation status of human iPS cells proceeded to iPS-HLCs...
April 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28338936/establishment-of-a-human-hepatocellular-cell-line-capable-of-maintaining-long-term-replication-of-hepatitis-b-virus
#15
Wan-Ling Yao, Sotaro Ikeda, Yuta Tsukamoto, Keiko Shindo, Yukie Otakaki, Mian Qin, Yoshikazu Iwasawa, Fumihiko Takeuchi, Yuki Kaname, Yu-Chi Chou, Chungming Chang, Koichi Watashi, Takaji Wakita, Takeshi Noda, Hiroki Kato, Takashi Fujita
Hepatitis B virus (HBV) is a virus whose replication cycle cannot be completely reproduced using cultured cell lines. Here, we report an engineered cell line capable of supporting the complete HBV life cycle. We generated HepG2 cells over-expressing the HBV entry receptor human NTCP (sodium taurocholate cotransporting polypeptide), and defective in RIG-I (retinoic acid-inducible gene-I)-like receptor signaling, by knocking down the IPS-1 (IFNβ-promoter stimulator-1) adaptor molecule. The resultant NtG20.i7 cells were susceptible to HBV, and its replication was detectable at 14 days post-infection and persisted for at least 35 days with a gradual increase of HBV core expression...
March 1, 2017: International Immunology
https://www.readbyqxmd.com/read/28213271/woodchuck-sodium-taurocholate-cotransporting-polypeptide-supports-low-level-hepatitis-b-and-d-virus-entry
#16
Liran Fu, Hongjie Hu, Yang Liu, Zhiyi Jing, Wenhui Li
Sodium taurocholate cotransporting polypeptide (NTCP) is the functional receptor for human hepatitis B virus (HBV) and its satellite hepatitis D virus (HDV). Species barriers to HBV/HDV infection are mainly determined at entry level by variations in the sequences of particular NTCP orthologs. In this study, we sought to determine whether the NTCP ortholog in woodchuck (Marmota monax), woodchuck NTCP (wNTCP) supports viral infection. We found that wNTCP is capable of supporting HBV/HDV infection in HepG2 cells, but to much lower extent than human NTCP (hNTCP), which is about 90% reduction of hNTCP...
May 2017: Virology
https://www.readbyqxmd.com/read/28195359/sodium-taurocholate-cotransporting-polypeptide-is-the-limiting-host-factor-of-hepatitis-b-virus-infection-in-macaque-and-pig-hepatocytes
#17
COMPARATIVE STUDY
Florian A Lempp, Ellen Wiedtke, Bingqian Qu, Pierre Roques, Isabelle Chemin, Florian W R Vondran, Roger Le Grand, Dirk Grimm, Stephan Urban
Infections with the human hepatitis B virus (HBV) and hepatitis D virus (HDV) depend on species-specific host factors like the receptor human sodium taurocholate cotransporting polypeptide (hNTCP). Complementation of mouse hepatocytes with hNTCP confers susceptibility to HDV but not HBV, indicating the requirement of additional HBV-specific factors. As an essential premise toward the establishment of an HBV-susceptible animal model, we investigated the role of hNTCP as a limiting factor of hepatocytes in commonly used laboratory animals...
September 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28125599/n-glycosylation-of-the-na-taurocholate-cotransporting-polypeptide-ntcp-determines-its-trafficking-and-stability-and-is-required-for-hepatitis-b-virus-infection
#18
Monique D Appelman, Anindita Chakraborty, Ulrike Protzer, Jane A McKeating, Stan F J van de Graaf
The sodium/bile acid cotransporter NTCP was recently identified as a receptor for hepatitis B virus (HBV). NTCP is glycosylated and the role of glycans in protein trafficking or viral receptor activity is not known. NTCP contains two N-linked glycosylation sites and asparagine amino acid residues N5 and N11 were mutated to a glutamine to generate NTCP with a single glycan (NTCP-N5Q or NTCP- N11Q) or no glycans (NTCP- N5,11Q). HepG2 cells expressing NTCP with a single glycan supported HBV infection at a comparable level to NTCP-WT...
2017: PloS One
https://www.readbyqxmd.com/read/28121714/hepatitis-delta-and-hiv-infection
#19
Vincent Soriano, Kenneth E Sherman, Pablo Barreiro
Viral liver diseases are frequent comorbidities and major contributors to death in HIV-positive individuals on antiretroviral therapy. Although cure of hepatitis C and control of hepatitis B with antivirals avert liver disease progression in most HIV-coinfected patients, the lack of satisfactory treatment for hepatitis delta virus (HDV) infection remains a major threat for developing cirrhosis and liver cancer in this population. In the European Union (EU) and North America, sexual contact has replaced injection drug use that has been the major transmission route for HDV in HIV-positive persons...
April 24, 2017: AIDS
https://www.readbyqxmd.com/read/28081591/new-perspectives-of-biomarkers-for-the-management-of-chronic-hepatitis-b
#20
REVIEW
Chih-Lin Lin, Jia-Horng Kao
With recent advances in molecular and genomic investigations, the impact of hepatitis B viral and host factors on the progression of chronic HBV infection has been explored. For viral factors, hepatitis B viral load is a strong predictor for liver disease progression. Hepatitis B viral kinetics appear to be important for successful anti-viral therapy. Serum HBsAg level serves as a complementary marker to viral load for the prediction of HBV-related adverse outcomes in patients with low viral load. In those with low viral load, high serum HBsAg level is associated with higher risks of cirrhosis and HCC...
December 2016: Clinical and Molecular Hepatology
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