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NTCP HBV

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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
#1
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
#2
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...
June 15, 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
#3
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...
June 9, 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
#4
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
#5
REVIEW
Ashish Kumar Vyas, Ankur Jindal, Syed Hissar, Gayatri Ramakrishna, Nirupama 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 development of chronic active hepatitis or acute on chronic liver failure. Strategies based on inhibition of viral replication (nucleoside analogues) or immune modulation (Interferons) as monotherapy, or in combination in sequential therapies, are currently being used globally for reducing HBV viral load and mediating HBsAg clearance...
April 7, 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
#6
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
#7
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
#8
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
#9
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 (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 towards the establishment for an HBV-susceptible animal model, we investigated the role of hNTCP as a limiting factor of hepatocytes in commonly used laboratory animals...
February 13, 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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/28047463/su-f-t-103-analysis-of-hepatitis-b-virus-reactivation-after-conformal-radiotherapy-in-patients-with-hepatocellular-carcinoma-using-the-lyman-ntcp-model
#13
Z Li, W Huang, H Li, B Li
PURPOSE: The aim of this research was to investigate the feasibility of Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) model in analyzing hepatitis B virus (HBV) reactivation in patients receiving conformal radiotherapy for patients with hepatocellular carcinoma (HCC). METHODS: Between June 2009 and June 2012, 108 HBV-related HCC patients (90 were specifically selected and 18 patients were excluded) treated with conformal RT at three centers were enrolled in this retrospective study...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/27975305/live-cell-imaging-confocal-microscopy-analysis-of-hbv-myr-pres1-peptide-binding-and-uptake-in-ntcp-gfp-expressing-hepg2-cells
#14
Alexander König, Dieter Glebe
To obtain basic knowledge about specific molecular mechanisms involved in the entry of pathogens into cells is the basis for establishing pharmacologic substances blocking initial viral binding, infection, and subsequent viral spread. Lack of information about key cellular factors involved in the initial steps of HBV infection has hampered the characterization of HBV binding and entry for decades. However, recently, the liver-specific sodium-dependent taurocholate cotransporting polypeptide (NTCP) has been discovered as a functional receptor for HBV and HDV, thus opening the field for new concepts of basic binding and entry of HBV and HDV...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27975304/hepatitis-b-virus-infection-of-heparg-cells-heparg-hntcp-cells-and-primary-human-hepatocytes
#15
Yi Ni, Stephan Urban
Investigations of virus-host interactions rely on suitable in vitro cell culture systems that efficiently support virus infection. Such systems should ideally provide conditions that resemble those of natural host cells, e.g., the cell-type specific signaling and metabolic pathways. For HBV infection, primary human hepatocytes (PHHs) are the most faithful system fulfilling these requirements but access to these cells is limited. Moreover, the reproducibility of experimental results depends on many factors including the preparation method or variability of the donors...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27975303/ntcp-reconstituted-in-vitro-hbv-infection-system
#16
Yinyan Sun, Yonghe Qi, Bo Peng, Wenhui Li
Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a functional receptor for hepatitis B virus (HBV). Expressing human NTCP in human hepatoma HepG2 cells (HepG2-NTCP) renders these cells susceptible for HBV infection. The HepG2-NTCP stably transfected cell line provides a much-needed and easily accessible platform for studying the virus. HepG2-NTCP cells could also be used to identify chemicals targeting key steps of the virus life cycle including HBV covalent closed circular (ccc) DNA, and enable the development of novel antivirals against the infection...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27890789/cyclosporin-derivatives-inhibit-hepatitis-b-virus-entry-without-interfering-with-ntcp-transporter-activity
#17
Satomi Shimura, Koichi Watashi, Kento Fukano, Michael Peel, Ann Sluder, Fumihiro Kawai, Masashi Iwamoto, Senko Tsukuda, Junko S Takeuchi, Takeshi Miyake, Masaya Sugiyama, Yuki Ogasawara, Sam-Yong Park, Yasuhito Tanaka, Hiroyuki Kusuhara, Masashi Mizokami, Camille Sureau, Takaji Wakita
BACKGROUND & AIMS: The sodium taurocholate co-transporting polypeptide (NTCP) is the main target of most hepatitis B virus (HBV) specific entry inhibitors. Unfortunately, these agents also block NTCP transport of bile acids into hepatocytes, and thus have the potential to cause adverse effects. We aimed to identify small molecules that inhibit HBV entry while maintaining NTCP transporter function. METHODS: We characterized a series of cyclosporine (CsA) derivatives for their anti-HBV activity and NTCP binding specificity using HepG2 cells overexpressing NTCP and primary human hepatocytes...
November 25, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/27863453/a-new-class-of-hepatitis-b-and-d-virus-entry-inhibitors-proanthocyanidin-and-its-analogs-that-directly-act-on-the-viral-large-surface-proteins
#18
Senko Tsukuda, Koichi Watashi, Taichi Hojima, Masanori Isogawa, Masashi Iwamoto, Katsumi Omagari, Ryosuke Suzuki, Hideki Aizaki, Soichi Kojima, Masaya Sugiyama, Akiko Saito, Yasuhito Tanaka, Masashi Mizokami, Camille Sureau, Takaji Wakita
Introduction of direct-acting antivirals against hepatitis C virus (HCV) has provided a revolutionary improvement in the treatment outcome. In contrast to HCV, however, the strategy for developing new antiviral agents against hepatitis B virus (HBV), especially viral-targeting compounds, is limited because HBV requires only four viral genes for its efficient replication/infection. Here, we identify an oligomeric flavonoid, proanthocyanidin (PAC) and its analogs, which inhibit HBV entry into host cells by targeting the HBV large surface protein (LHBs)...
April 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27784961/elucidation-of-the-early-infection-machinery-of-hepatitis-b-virus-by-using-bio-nanocapsule
#19
REVIEW
Qiushi Liu, Masaharu Somiya, Shun'ichi Kuroda
Currently, hepatitis B virus (HBV), upon attaching to human hepatocytes, is considered to interact first with heparan sulfate proteoglycan (HSPG) via an antigenic loop of HBV envelope S protein. Then, it is promptly transferred to the sodium taurocholate cotransporting polypeptide (NTCP) via the myristoylated N-terminal sequence of pre-S1 region (from Gly-2 to Gly-48, HBV genotype D), and it finally enters the cell by endocytosis. However, it is not clear how HSPG passes HBV to NTCP and how NTCP contributes to the cellular entry of HBV...
October 14, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27783949/solute-carrier-ntcp-regulates-innate-antiviral-immune-responses-targeting-hepatitis-c-virus-infection-of-hepatocytes
#20
Eloi R Verrier, Che C Colpitts, Charlotte Bach, Laura Heydmann, Laetitia Zona, Fei Xiao, Christine Thumann, Emilie Crouchet, Raphaël Gaudin, Camille Sureau, François-Loïc Cosset, Jane A McKeating, Patrick Pessaux, Yujin Hoshida, Catherine Schuster, Mirjam B Zeisel, Thomas F Baumert
Chronic hepatitis B, C, and D virus (HBV, HCV, and HDV) infections are the leading causes of liver disease and cancer worldwide. Recently, the solute carrier and sodium taurocholate co-transporter NTCP has been identified as a receptor for HBV and HDV. Here, we uncover NTCP as a host factor regulating HCV infection. Using gain- and loss-of-function studies, we show that NTCP mediates HCV infection of hepatocytes and is relevant for cell-to-cell transmission. NTCP regulates HCV infection by augmenting the bile-acid-mediated repression of interferon-stimulated genes (ISGs), including IFITM3...
October 25, 2016: Cell Reports
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