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Sodium taurocholate cotransporting polypeptide

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https://www.readbyqxmd.com/read/29290974/sodium-taurocholate-cotransporting-polypeptide-ntcp-deficiency-identification-of-a-novel-slc10a1-mutation-in-two-unrelated-infants-presenting-with-neonatal-indirect-hyperbilirubinemia-and-remarkable-hypercholanemia
#1
Jian-Wu Qiu, Mei Deng, Ying Cheng, Raza-Muhammad Atif, Wei-Xia Lin, Li Guo, Hua Li, Yuan-Zong Song
Sodium taurocholate cotransporting polypeptide (NTCP) is encoded by the gene SLC10A1 and expressed in the basolateral membrane of the hepatocyte, functioning to uptake bile acids from plasma. Although SLC10A1 has been cloned and NTCP function studied intensively for years, clinical description of NTCP deficiency remains rather limited. This study reported the genotypic and phenotypic features of two neonatal patients with NTCP deficiency. They both presented with neonatal indirect hyperbilirubinemia and remarkable hypercholanemia, and harbored the SLC10A1 variants c...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29285260/genetic-variations-of-ntcp-are-associated-with-susceptibility-to-hbv-infection-and-related-hepatocellular-carcinoma
#2
Peng Wang, Ruidong Mo, Rongtao Lai, Yumin Xu, Jie Lu, Gangde Zhao, Yuhan Liu, Zhujun Cao, Xiaolin Wang, Ziqiang Li, Lanyi Lin, Huijuan Zhou, Wei Cai, Hui Wang, Shisan Bao, Xiaogang Xiang, Qing Xie
Sodium taurocholate cotransporting polypeptide (NTCP), encoded by gene SLC10A1, is a receptor for hepatitis B virus (HBV). The aim of the current study was to investigate the role of NTCP polymorphisms in HBV susceptibility, cirrhosis and hepatocarcinogenesis. A total 1221 cases [including 866 chronic hepatitis B (CHB), 238 liver cirrhosis (LC), 117 hepatocellular carcinoma (HCC) patients] and 1232 healthy controls (HCs) were recruited, and 6 single nucleotide polymorphisms (SNPs) were genotyped. Meta-analysis was executed among 14591 CHBs and 12396 HCs to determine the association between NTCP polymorphisms and HBV infection, cirrhosis or hepatocarcinogenesis...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29247233/effect-of-s267f-variant-of-ntcp-on-the-patients-with-chronic-hepatitis-b
#3
Hye Won Lee, Hye Jung Park, Bora Jin, Mehrangiz Dezhbord, Do Young Kim, Kwang-Hyub Han, Wang-Shick Ryu, Seungtaek Kim, Sang Hoon Ahn
Sodium taurocholate cotransporting polypeptide (NTCP) was identified as an entry receptor for hepatitis B virus (HBV) infection. The substitution of serine at position 267 of NTCP with phenylalanine (S267F) is an Asian-specific variation that hampers HBV entry in vitro. In this study, we aimed to evaluate the prevalence of S267F polymorphism in Korean patients with chronic hepatitis B (CHB) and its association with disease progression and potential viral evolution in the preS1 domain of HBV. We found that the frequency of the S267F variant of NTCP in CHB patients and controls was 2...
December 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29247188/hepatocytic-expression-of-human-sodium-taurocholate-cotransporting-polypeptide-enables-hepatitis-b-virus-infection-of-macaques
#4
Benjamin J Burwitz, Jochen M Wettengel, Martin A Mück-Häusl, Marc Ringelhan, Chunkyu Ko, Marvin M Festag, Katherine B Hammond, Mina Northrup, Benjamin N Bimber, Thomas Jacob, Jason S Reed, Reed Norris, Byung Park, Sven Moller-Tank, Knud Esser, Justin M Greene, Helen L Wu, Shaheed Abdulhaqq, Gabriela Webb, William F Sutton, Alex Klug, Tonya Swanson, Alfred W Legasse, Tania Q Vu, Aravind Asokan, Nancy L Haigwood, Ulrike Protzer, Jonah B Sacha
Hepatitis B virus (HBV) is a major global health concern, and the development of curative therapeutics is urgently needed. Such efforts are impeded by the lack of a physiologically relevant, pre-clinical animal model of HBV infection. Here, we report that expression of the HBV entry receptor, human sodium-taurocholate cotransporting polypeptide (hNTCP), on macaque primary hepatocytes facilitates HBV infection in vitro, where all replicative intermediates including covalently closed circular DNA (cccDNA) are present...
December 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/29217749/hepatitis-delta-virus-persists-during-liver-regeneration-and-is-amplified-through-cell-division-both-in-vitro-and-in-vivo
#5
Katja Giersch, Oliver D Bhadra, Tassilo Volz, Lena Allweiss, Kristoffer Riecken, Boris Fehse, Ansgar W Lohse, Joerg Petersen, Camille Sureau, Stephan Urban, Maura Dandri, Marc Lütgehetmann
OBJECTIVE: Hepatitis delta virus (HDV) was shown to persist for weeks in the absence of HBV and for months after liver transplantation, demonstrating the ability of HDV to persevere in quiescent hepatocytes. The aim of the study was to evaluate the impact of cell proliferation on HDV persistence in vitro and in vivo. DESIGN: Genetically labelled human sodium taurocholate cotransporting polypeptide (hNTCP)-transduced human hepatoma(HepG2) cells were infected with HBV/HDV and passaged every 7 days for 100 days in the presence of the entry inhibitor Myrcludex-B...
December 7, 2017: Gut
https://www.readbyqxmd.com/read/29216213/a-multi-scale-spatial-model-of-hepatitis-b-viral-dynamics
#6
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/29192196/a-robust-cell-culture-system-supporting-the-complete-life-cycle-of-hepatitis-b-virus
#7
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/29089529/heparin-at-physiological-concentration-can-enhance-peg-free-in-vitro-infection-with-human-hepatitis-b-virus
#8
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/28962642/upregulation-of-sodium-taurocholate-cotransporter-polypeptide-during-hepatogenic-differentiation-of-umbilical-cord-matrix-mesenchymal-stem-cells-facilitates-hepatitis-b-entry
#9
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/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/28852124/oxidative-stress-and-immune-responses-during-hepatitis-c-virus-infection-in-tupaia-belangeri
#12
Mohammad Enamul Hoque Kayesh, Sayeh Ezzikouri, Takahiro Sanada, Haiying Chi, Yukiko Hayashi, Khadija Rebbani, Bouchra Kitab, Aya Matsuu, Noriaki Miyoshi, Tsunekazu Hishima, Michinori Kohara, Kyoko Tsukiyama-Kohara
Hepatitis C virus (HCV) is a leading cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma. To address the molecular basis of HCV pathogenesis using tupaias (Tupaia belangeri), we characterized host responses upon HCV infection. Adult tupaias were infected with HCV genotypes 1a, 1b, 2a, or 4a. Viral RNA, alanine aminotransferase, anti-HCV core and anti-nonstructural protein NS3 antibody titres, reactive oxygen species (ROS), and anti-3β-hydroxysterol-Δ24reductase (DHCR24) antibody levels were measured at 2-week intervals from 0 to 41 weeks postinfection...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28835676/homozygous-p-ser267phe-in-slc10a1-is-associated-with-a-new-type-of-hypercholanemia-and-implications-for-personalized-medicine
#13
Ruihong Liu, Chuming Chen, Xuefeng Xia, Qijun Liao, Qiong Wang, Paul J Newcombe, Shuhua Xu, Minghui Chen, Yue Ding, Xiaoying Li, Zhihong Liao, Fucheng Li, Minlian Du, Huaiqiu Huang, Ruimin Dong, Weiping Deng, Ye Wang, Binghui Zeng, Qihao Pan, Danhua Jiang, Hao Zeng, Pak Sham, Yingnan Cao, Patrick H Maxwell, Zhi-Liang Gao, Liang Peng, Yiming Wang
SLC10A1 codes for the sodium-taurocholate cotransporting polypeptide (NTCP), which is a hepatocellular transporter for bile acids (BAs) and the receptor for hepatitis B and D viruses. NTCP is also a target of multiple drugs. We aimed to evaluate the medical consequences of the loss of function mutation p.Ser267Phe in SLC10A1. We identified eight individuals with homozygous p.Ser267Phe mutation in SLC10A1 and followed up for 8-90 months. We compared their total serum BAs and 6 species of BAs with 170 wild-type and 107 heterozygous healthy individuals...
August 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28802063/hepatitis-b-virus-pregenomic-rna-in-hepatocellular-carcinoma-a-nosological-and-prognostic-determinant
#14
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
#15
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/28624460/identification-of-kx2-391-as-an-inhibitor-of-hbv-transcription-by-a-recombinant-hbv-based-screening-assay
#16
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/28559272/an-effective-antiviral-approach-targeting-hepatitis-b-virus-with-njk14047-a-novel-and-selective-biphenyl-amide-p38-mitogen-activated-protein-kinase-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 remains 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...
August 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28551415/interferon-%C3%AE-response-is-impaired-by-hepatitis-b-virus-infection-in-tupaia-belangeri
#18
Mohammad Enamul Hoque Kayesh, Sayeh Ezzikouri, Haiying Chi, Takahiro Sanada, Naoki Yamamoto, Bouchra Kitab, Takumi Haraguchi, Rika Matsuyama, Chimène Nze Nkogue, Hitoshi Hatai, Noriaki Miyoshi, Shuko Murakami, Yasuhito Tanaka, Jun-Ichiro Takano, Yumiko Shiogama, Yasuhiro Yasutomi, Michinori Kohara, Kyoko Tsukiyama-Kohara
To date, the chimpanzee has been used as the natural infection model for hepatitis B virus (HBV). However, as this model is very costly and difficult to use because of ethical and animal welfare issues, we aimed to establish the tupaia (Tupaia belangeri) as a new model for HBV infection and characterized its intrahepatic innate immune response upon HBV infection. First, we compared the propagation of HBV genotypes A2 and C in vivo in tupaia hepatocytes. At 8-10days post infection (dpi), the level of HBV-A2 propagation in the tupaia liver was found to be higher than that of HBV-C...
May 25, 2017: Virus Research
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/28374759/human-induced-pluripotent-stem-cell-derived-hepatocyte-like-cells-as-an-in-vitro-model-of-human-hepatitis-b-virus-infection
#20
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
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