Neuropilin-1 is a novel host factor facilitating the entry of hepatitis B virus
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE264335 | GEO | 2026/05/31
REPOSITORIES: GEO
Similar Datasets
Project description:miR-6126 downregulated expression level of sodium taurocholate cotransporting polypeptide (NTCP), a host cell receptor required for hepatitis B virus (HBV) entry.
2022-08-01 | GSE180543 | GEO
Project description:Chronic hepatitis B, C and D virus (HBV, HCV, HDV) infections are leading causes of liver disease and cancer worldwide. Although these viruses differ markedly in their life cycle and genomic organization, they exclusively infect hepatocytes. Recently, the sodium taurocholate cotransporting polypeptide (NTCP) was identified as the first functional receptor for HBV and HDV. Here, we report that NTCP also facilitates HCV entry into human hepatocytes, by augmenting the bile acid-mediated repression of IFN-stimulated genes (ISGs), including IFITM2 and IFITM3, to increase the susceptibility of cells to HCV entry. Furthermore, an HBV-derived preS1 peptide, known to bind NTCP and to inhibit bile acid uptake and HBV infection, inhibits HCV entry by enhancing the expression of ISGs. Our study highlights NTCP as a novel player linking bile acid metabolism to the interferon response in hepatocytes and establishes a role for NTCP in the entry process of multiple hepatotropic viruses, via distinct mechanisms. Collectively, these findings enhance our understanding of hepatitis virus-host interactions and suggest NTCP as an attractive antiviral target for HBV/HCV co-infection. Transcriptome profiling by DNA microarray of Huh7.5.1 cells transduced to express NTCP.
2016-10-25 | E-GEOD-79089 | biostudies-arrayexpress
Project description:Aim: Hepatitis B virus (HBV) infection is one of the most serious global health problems. Our previous study revealed that an increase in the miR-6126 serum level over one year of pegylated interferon therapy predicted a decrease in hepatitis B surface (HBs) antigens. We aimed to clarify whether miR-6126 downregulated the expression level of sodium taurocholate cotransporting polypeptide (NTCP), a host cell receptor required for HBV entry. Methods: HepG2-NTCP and PXB cells were utilized to evaluate the expression level of NTCP after transfection with miR-6126. The protein expression level of NTCP was evaluated using Western blot analysis and immunostaining. The expression profile of messenger RNAs was evaluated using next-generation sequencing to search for direct targets of miR-6126.
2021-12-28 | GSE192617 | GEO
Project description:Chronic hepatitis B, C and D virus (HBV, HCV, HDV) infections are leading causes of liver disease and cancer worldwide. Although these viruses differ markedly in their life cycle and genomic organization, they exclusively infect hepatocytes. Recently, the sodium taurocholate cotransporting polypeptide (NTCP) was identified as the first functional receptor for HBV and HDV. Here, we report that NTCP also facilitates HCV entry into human hepatocytes, by augmenting the bile acid-mediated repression of IFN-stimulated genes (ISGs), including IFITM2 and IFITM3, to increase the susceptibility of cells to HCV entry. Furthermore, an HBV-derived preS1 peptide, known to bind NTCP and to inhibit bile acid uptake and HBV infection, inhibits HCV entry by enhancing the expression of ISGs. Our study highlights NTCP as a novel player linking bile acid metabolism to the interferon response in hepatocytes and establishes a role for NTCP in the entry process of multiple hepatotropic viruses, via distinct mechanisms. Collectively, these findings enhance our understanding of hepatitis virus-host interactions and suggest NTCP as an attractive antiviral target for HBV/HCV co-infection.
2016-10-25 | GSE79089 | GEO
Project description:Chronic hepatitis B, C and D virus (HBV, HCV, HDV) infections are leading causes of liver disease and cancer worldwide. Although these viruses differ markedly in their life cycle and genomic organization, they exclusively infect hepatocytes. Recently, the sodium taurocholate cotransporting polypeptide (NTCP) was identified as the first functional receptor for HBV and HDV. Here, we report that NTCP also facilitates HCV entry into human hepatocytes, by augmenting the bile acids-mediated repression of IFN-stimulated genes (ISGs), including IFITM2 and IFITM3, to increase the susceptibility of cells to HCV entry. Furthermore, an HBV-derived preS1 peptide, known to bind NTCP and to inhibit bile acids uptake and HBV infection, inhibits HCV entry by enhancing the expression of ISGs. Our study highlights NTCP as a novel player linking bile acids metabolism to the interferon response in hepatocytes and establishes a role for NTCP in the entry process of multiple hepatotropic viruses, via distinct mechanisms. Collectively, these findings enhance our understanding of hepatitis virus-host interactions and suggest NTCP as an attractive antiviral target for HBV/HCV co-infection.
2016-10-25 | GSE85091 | GEO
Project description:Chronic hepatitis B virus (HBV) infections represent a major global health burden requiring effective therapeutic interventions. This study investigates the antiviral potential of microRNAs (miRNAs) targeting the HBV entry receptor, sodium-taurocholate cotransporting polypeptide (NTCP). Using an experimental model of primary human hepatocytes (PHHs), we highlighted a set of candidate antiviral miRNAs induced by interferon (IFN) alpha analog treatment. Notably, predictive analysis identified miR-29b-1-5p as interacting with the 3’-untranslated region (3’-UTR) of NTCP, suggesting a post-transcriptional regulatory mechanism. Functional analysis indicated that miR-29b-1-5p directly targeted the NTCP 3’-UTR, leading to significant inhibition of NTCP transcripts. Consistently, hepatocytes overexpressing miR-29b-1-5p showed a remarkable reduction in HBV genome levels after infection. A rescue assay demonstrated that miR-29b-1-5p anti-HBV effect was specifically mediated by NTCP targeting. In summary, these findings underscore the therapeutic potential of miR-29b-1-5p against HBV, advocating for further exploration of miRNA-based therapies in the treatment of human viral infections.
2024-04-26 | GSE264652 | GEO
Project description:Hepatitis B virus (HBV) infection remains a major global health challenge. While sodium taurocholate co-transporting polypeptide (NTCP) is the primary receptor for HBV entry, the molecular mechanisms regulating NTCP-mediated viral entry remain incompletely understood. Here, we identified CD46 as a crucial regulatory factor for NTCP membrane expression. We found that CD46 interacted with NTCP in cis at the plasma membrane through proximity-based labeling screening. The depletion of CD46 significantly reduced cell-surface NTCP levels and HBV infection in hepatocytes. Anti-CD46 monoclonal antibodies, particularly clone E4.3, inhibited HBV infection by triggering NTCP internalization from the plasma membrane to intracellular vesicles. The antiviral effect of CD46 antibodies was also confirmed in primary human hepatocytes. Our study reveals a previously unknown cis-acting mechanism regulating NTCP-mediated HBV entry and suggests CD46 as a potential therapeutic target for HBV infection.
2026-01-13 | PXD065037 | JPOST Repository
Project description:Chronic hepatitis B virus (HBV) infections remain a health burden affecting ~250 million people worldwide. Thus far, available interferon-alpha (IFNα)-based therapies have shown unsatisfactory cure rates, and alternative therapeutic molecules are still required. However, their development has been hampered because accessible cell models supporting relevant HBV replication and appropriate antiviral activity are lacking. Strategies that reverse epigenetic alterations offer a unique opportunity for cell reprogramming, which is valuable for restoring altered cellular functions in human cell lines. This work aimed to investigate the feasibility of converting HepG2 cells that stably overexpress the HBV entry receptor (sodium/taurocholate cotransporting polypeptide, NTCP) toward IFNα-responsive cells using epigenetic reprogramming. Herein, we showed that an epigenetic regimen with non-cytotoxic doses of the demethylating compound 5-azacytidine restored the anti-HBV action of IFNα in epigenetically reprogrammed HepG2-NTCP-C4 cells, named REP-HepG2-NTCP cells. Thus, a significant inhibition in HBV DNA levels was measured in REP-HepG2-NTCP cells after IFNα treatment. This inhibitory effect was associated with the enhancement of IFNα-mediated induction of critical interferon-stimulated genes (ISGs), which was limited in non-reprogrammed cells. In particular, our data indicated that re-expression of 2’-5’-oligoadenylate synthetase 1 (OAS1) and interferon regulatory factor 9 (IRF9) was the result of an epigenetically driven unmasking of these genes in reprogrammed cells. At last, we evaluated the therapeutic potential of the IFN analog CDM-3008 in REP-HepG2-NTCP cells and demonstrated the efficiency of this chemical compound in triggering ISG induction and HBV inhibition. In summary, this study shows that epigenetic reprogramming promotes the IFNα response in HBV-infected cells and is potentially attractive for cell-based experimental screening of IFN-like compounds.
2020-11-24 | GSE160648 | GEO
Project description:Sodium taurocholate co-transporting polypeptide (NTCP) is a liver specific bile acid (BA) transporter; this transporter also serves as a functional receptor for hepatitis B virus (HBV) and hepatitis D virus (HDV). Here, we generated mouse models to investigate the role of NTCP in hepatocarcinogenesis. We report that NTCP-deficient (Slc10a1-/-) mice with long-term hypercholanemia do not develop spontaneous hepatocellular carcinoma (HCC). Using a diethylnitrosamine (DEN)-induced mouse model of HCC, we found that Slc10a1-/- mice exhibited fewer liver tumors, while transgenic mice constitutively overexpressing mouse NTCP in hepatocytes Tg(mNTCP-C9) experienced increased tumor burdens. Intriguingly, the subset of male Slc10a1-/- mice with hypercholanemia exhibited a hepatic female-biased gene expression. Importantly, a majority of the human homologs of genes with significantly hepatic female-biased expression were found to be correlated with improved prognosis in human patients with liver cancer. Our findings indicate that pharmacological manipulation of NTCP function can have a clinical impact on decreasing risk of development or decreasing risk of death liver cancer.
2025-08-01 | GSE155870 | GEO
Project description:Impaired bile flow (cholestasis) leads to transcriptional downregulation of the bile acid importer Na+-taurocholate co-transporting protein (NTCP) and to ER-stress in the liver. Here, we show that ER-stress induction strongly reduces NTCP protein expression, plasma membrane abundance and NTCP-mediated bile acid uptake. This is not controlled via a single specific UPR-pathway but mainly depends on the interaction of NTCP with calnexin, an ER chaperone involved in folding of N-glycosylated proteins. In mice, expression of both Ntcp and calnexin was reduced by thapsigargin-induced ER-stress. Calnexin downregulation in HepG2 and U2OS cells results in a decreased NTCP expression and a reduced bile acid uptake. Calreticulin shows partial functional redundancy with calnexin as it also interacts with NTCP, and is downregulated upon ER-stress, but specifically in calnexin-depleted cells. In conclusion, ER stress-induced downregulation of calnexin provides an additional mechanism to dampen NTCP-mediated bile acid uptake during cholestasis.
2019-01-07 | PXD007948 | Pride