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NTCP HBV

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https://www.readbyqxmd.com/read/28081591/new-perspectives-of-biomarkers-for-the-management-of-chronic-hepatitis-b
#1
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
#2
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
#3
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
#4
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
#5
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-the-ntcp-transporter
#6
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: Most of the specific inhibitors of hepatitis B virus (HBV) entry, including myrcludex-B and cyclosporin A (CsA), target an HBV entry receptor, sodium taurocholate cotransporting polypeptide (NTCP). As all these agents have capacities to impair the NTCP transporter activity for bile acid uptake and thus may cause significant adverse effects, we aim to identify small molecules that inhibit HBV entry but least affecting the NTCP transporter function. METHODS: We focused on derivatives of CsA, which originally inhibited both HBV entry and NTCP-mediated bile acid uptake, to analyze the possibility to distinguish these two activities...
November 24, 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
#7
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 since 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)...
November 18, 2016: 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
#8
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
#9
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
https://www.readbyqxmd.com/read/27783675/dna-polymerase-%C3%AE%C2%BA-is-a-key-cellular-factor-for-the-formation-of-covalently-closed-circular-dna-of-hepatitis-b-virus
#10
Yonghe Qi, Zhenchao Gao, Guangwei Xu, Bo Peng, Chenxuan Liu, Huan Yan, Qiyan Yao, Guoliang Sun, Yang Liu, Dingbin Tang, Zilin Song, Wenhui He, Yinyan Sun, Ju-Tao Guo, Wenhui Li
Hepatitis B virus (HBV) infection of hepatocytes begins by binding to its cellular receptor sodium taurocholate cotransporting polypeptide (NTCP), followed by the internalization of viral nucleocapsid into the cytoplasm. The viral relaxed circular (rc) DNA genome in nucleocapsid is transported into the nucleus and converted into covalently closed circular (ccc) DNA to serve as a viral persistence reservoir that is refractory to current antiviral therapies. Host DNA repair enzymes have been speculated to catalyze the conversion of rcDNA to cccDNA, however, the DNA polymerase(s) that fills the gap in the plus strand of rcDNA remains to be determined...
October 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27635243/recent-advances-in-understanding-and-diagnosing-hepatitis-b-virus-infection
#11
REVIEW
Slim Fourati, Jean-Michel Pawlotsky
Hepatitis B virus (HBV) infects approximately 240 million individuals worldwide. Recent advances in the virology, immunopathogenesis, and diagnosis of HBV infection are summarized in this review article. The identification of a hepatocyte-specific cellular receptor for HBV, the sodium taurocholate co-transporting polypeptide (NTCP), made it possible to develop reliable cell culture systems and better understand the early steps of the viral lifecycle. Viral and host factors involved in covalently closed circular DNA synthesis, stability, and transcriptional regulation have also been identified and provide potential targets for new drugs...
2016: F1000Research
https://www.readbyqxmd.com/read/27568223/immunotherapy-with-the-pres-based-grass-pollen-allergy-vaccine-bm32-induces-antibody-responses-protecting-against-hepatitis-b-infection
#12
Carolin Cornelius, Katrin Schöneweis, Fanny Georgi, Milena Weber, Verena Niederberger, Petra Zieglmayer, Katarzyna Niespodziana, Michael Trauner, Harald Hofer, Stephan Urban, Rudolf Valenta
BACKGROUND: We have constructed and clinically evaluated a hypoallergenic vaccine for grass pollen allergy, BM32, which is based on fusion proteins consisting of peptides from the IgE binding sites of the major grass pollen allergens fused to preS (preS1+preS2), a domain of the hepatitis B virus (HBV) large envelope protein which mediates the viral attachment and entry. Aim of this study was the characterization of the HBV-specific immune response induced by vaccination of allergic patients with BM32 and the investigation of the vaccines' potential to protect against infection with HBV...
September 2016: EBioMedicine
https://www.readbyqxmd.com/read/27534692/hepatitis-delta-virus-insights-into-a-peculiar-pathogen-and-novel-treatment-options
#13
REVIEW
Florian A Lempp, Yi Ni, Stephan Urban
Chronic hepatitis D is the most severe form of viral hepatitis, affecting ∼20 million HBV-infected people worldwide. The causative agent, hepatitis delta virus (HDV), is a unique human pathogen: it is the smallest known virus; it depends on HBV to disseminate its viroid-like RNA; it encodes only one protein (HDAg), which has both structural and regulatory functions; and it replicates using predominantly host proteins. The failure of HBV-specific nucleoside analogues to suppress the HBV helper function, and the limitations of experimental systems to study the HDV life cycle, have impeded the development of HDV-specific drugs...
October 2016: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/27515132/inhibitory-effect-of-cdk9-inhibitor-fit-039-on-hepatitis-b-virus-propagation
#14
Tomohisa Tanaka, Kaori Okuyama-Dobashi, Shuko Murakami, Wenjia Chen, Toru Okamoto, Keiji Ueda, Takamitsu Hosoya, Yoshiharu Matsuura, Akihide Ryo, Yasuhito Tanaka, Masatoshi Hagiwara, Kohji Moriishi
Current therapies for hepatitis B virus (HBV) cannot completely eliminate the HBV genome because of the stable population of covalently closed circular DNA (cccDNA) and so on. FIT-039, which is a cyclin-dependent kinase (CDK) 9 inhibitor, is known to suppress the replication of several DNA viruses including HSV, HPV and human adenovirus. In this study, we investigated the antiviral effect of FIT-039 on HBV infection. HepG2 cells expressing human sodium taurocholate cotransporting polypeptide (HepG2/NTCP cells) were infected with HBV in the presence of FIT-039...
September 2016: Antiviral Research
https://www.readbyqxmd.com/read/27507206/screening-and-verifying-potential-ntcp-inhibitors-from-herbal-medicinal-ingredients-using-the-llc-pk1-cell-model-stably-expressing-human-ntcp
#15
Zhuo-Wei Shen, Meng-Yue Luo, Hai-Hong Hu, Hui Zhou, Hui-Di Jiang, Lu-Shan Yu, Su Zeng
NTCP is specifically expressed on the basolateral membrane of hepatocytes, participating in the enterohepatic circulation of bile salts, especially conjugated bile salts, to maintain bile salts homeostasis. In addition, recent studies have found that NTCP is a functional receptor of HBV and HDV. Therefore, it is important to study the interaction between drugs and NTCP and identify the inhibitors/substrates of NTCP. In the present study, a LLC-PK1 cell model stably expressing human NTCP was established, which was simple and suitable for high throughput screening, and utilized to screen and verify the potential inhibitors of NTCP from 102 herbal medicinal ingredients...
July 2016: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/27491457/genetic-variants-in-the-regulatory-region-of-slc10a1-are-not-associated-with-the-risk-of-hepatitis-b-virus-infection-and-clearance
#16
Xueqin Chen, Ying Wang, Xiaohua Chen, Kailiang Cheng, Jiaoyuan Li, Jiao Lou, Juntao Ke, Yang Yang, Yajie Gong, Ying Zhu, Li Wang, Rong Zhong
The Na/taurocholate cotransporter NTCP (encoded by SLC10A1) was identified as a cellular entry receptor for the human hepatitis B virus (HBV), advancing our understanding of the molecular mechanism of HBV infection. An alternative hypothesis was put forward that regulatory variants in SLC10A1 might play an important role in HBV susceptibility by potentially influencing expression levels of NTCP. The three regulatory SNPs (rs8011311, rs7154439, rs111409076) were genotyped in 1023 HBV-persistent carriers, 735 subjects with HBV natural clearance and 732 HBV marker-negative subjects in a Han Chinese population...
October 2016: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/27466423/modification-of-three-amino-acids-in-sodium-taurocholate-cotransporting-polypeptide-renders-mice-susceptible-to-infection-with-hepatitis-d-virus-in-vivo
#17
Wenhui He, Zhiliang Cao, Fengfeng Mao, Bijie Ren, Yunfei Li, Dan Li, Huiyu Li, Bo Peng, Huan Yan, Yonghe Qi, Yinyan Sun, Fengchao Wang, Jianhua Sui, Wenhui Li
UNLABELLED: Sodium taurocholate cotransporting polypeptide (NTCP) was identified as a functional receptor for hepatitis D virus (HDV) and its helper hepatitis B virus (HBV). In cultured cell lines, HDV infection through mouse NTCP is restricted by residues 84 to 87 of the receptor. This study shows that mice with these three amino acids altered their corresponding human residues (H84R, T86K, and S87N) in endogenous mouse NTCP support de novo HDV infection in vivo HDV infection was documented by the presence of replicative forms of HDV RNA and HDV proteins in liver cells at day 6 after viral inoculation...
October 1, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27447092/hbv-cure-why-how-when
#18
REVIEW
Massimo Levrero, Barbara Testoni, Fabien Zoulim
Current HBV treatments control replication and liver disease progression in the vast majority of treated patients. However, HBV patients often require lifelong therapies due to the persistence of transcriptionally active viral cccDNA mini-chromosome in the nucleus, which is not directly targeted by current antiviral therapies. A true complete cure of HBV would require clearance of intranuclear cccDNA from all infected hepatocytes. An intermediate but still relevant step forward that would allow treatment cessation would be reaching a functional cure, equivalent to resolved acute infection, with a durable HBsAg loss±anti-HBs seroconversion, undetectable serum DNA and persistence of cccDNA in a transcriptionally inactive status...
June 2016: Current Opinion in Virology
https://www.readbyqxmd.com/read/27420796/cellular-uptake-of-hepatitis-b-virus-envelope-l-particles-is-independent-of-sodium-taurocholate-cotransporting-polypeptide-but-dependent-on-heparan-sulfate-proteoglycan
#19
Masaharu Somiya, Qiushi Liu, Nobuo Yoshimoto, Masumi Iijima, Kenji Tatematsu, Tadashi Nakai, Toshihide Okajima, Kazuyuki Kuroki, Keiji Ueda, Shun'ichi Kuroda
Sodium taurocholate cotransporting polypeptide (NTCP) was recently discovered as a hepatitis B virus (HBV) receptor, however, the detailed mechanism of HBV entry is not yet fully understood. We investigated the cellular entry pathway of HBV using recombinant HBV surface antigen L protein particles (bio-nanocapsules, BNCs). After the modification of L protein in BNCs with myristoyl group, myristoylated BNCs (Myr-BNCs) were found to bind to NTCP in vitro, and inhibit in vitro HBV infection competitively, suggesting that Myr-BNCs share NTCP-dependent infection machinery with HBV...
October 2016: Virology
https://www.readbyqxmd.com/read/27386799/human-induced-pluripotent-stem-cell-derived-hepatic-cell-lines-as-a-new-model-for-host-interaction-with-hepatitis-b-virus
#20
Shun Kaneko, Sei Kakinuma, Yasuhiro Asahina, Akihide Kamiya, Masato Miyoshi, Tomoyuki Tsunoda, Sayuri Nitta, Yu Asano, Hiroko Nagata, Satoshi Otani, Fukiko Kawai-Kitahata, Miyako Murakawa, Yasuhiro Itsui, Mina Nakagawa, Seishin Azuma, Hiromitsu Nakauchi, Hironori Nishitsuji, Saneyuki Ujino, Kunitada Shimotohno, Masashi Iwamoto, Koichi Watashi, Takaji Wakita, Mamoru Watanabe
Hepatitis B virus (HBV) is not eradicated by current antiviral therapies due to persistence of HBV covalently closed circular DNA (cccDNA) in host cells, and thus development of novel culture models for productive HBV infection is urgently needed, which will allow the study of HBV cccDNA eradication. To meet this need, we developed culture models of HBV infection using human induced pluripotent stem cell-derived hepatocyte lineages, including immature proliferating hepatic progenitor-like cell lines (iPS-HPCs) and differentiated hepatocyte-like cells (iPS-Heps)...
2016: Scientific Reports
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