ArticleEmerging microbes & infections2019
Down-regulation of cell membrane localized NTCP expression in proliferating hepatocytes prevents hepatitis B virus infection.
Article in Emerging microbes & infections, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 62 citations in OpenAlex.
- CD46 regulates hepatitis B virus entry by modulating cell-surface NTCP levels through cis-interaction.Journal of molecular cell biology · 2026Article
- Clinical significance and mutation analysis of HBsAg and Anti-HBs coexistence in Chronic Hepatitis B.Virus research · 2026Article
- Younger age predicts increased HBsAg loss in children with chronic hepatitis B on antiviral therapy: A systematic review and meta-analysis.Infectious diseases & immunity · 2026Article
- [Comparison of antiviral efficacy of nucleos(t)ide analogue monotherapy and its combination with interferon-α in children 1-6 years-old with HBeAg-positive chronic hepatitis B].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Article
- Article
- Unveiling low level viremia in chronic hepatitis B: challenges and new horizons.Frontiers in cellular and infection microbiology · 2025Review
- Adding pegylated interferon-α to nucleos(t)ide analogs improves HBsAg clearance in chronic hepatitis B with low-level viremia.Frontiers in medicine · 2025Article
- The loss of hepatitis B virus receptor NTCP/SLC10A1 in human liver cancer cells is due to epigenetic silencing.Journal of virology · 2024Article
- STING-mediated IL-6 Inhibits OATP1B1 Expression via the TCF4 Signaling Pathway in Cholestasis.Journal of clinical and translational hepatology · 2024Article
- Review
- Hepatitis B cure: Current situation and prospects.World journal of hepatology · 2024Review
- Association of chronic hepatitis B infection with hepatic steatosis and injury in nonalcoholic fatty liver disease children.BMC gastroenterology · 2024Article
- Dysfunction and regulatory interplay of T and B cells in chronic hepatitis B: immunotherapy and emerging antiviral strategies.Frontiers in cellular and infection microbiology · 2024Review
- The Culprit Behind HBV-Infected Hepatocytes: NTCP.Drug design, development and therapy · 2024Review
- Interferon-Free Regimens and Direct-Acting Antiviral Agents for Delta Hepatitis: Are We There Yet?Current issues in molecular biology · 2023Review
- Targeted viral adaptation generates a simian-tropic hepatitis B virus that infects marmoset cells.Nature communications · 2023Article
- CDK4/6 inhibitor palbociclib promotes SARS-CoV-2 cell entry by down-regulating SKP2 dependent ACE2 degradation.Antiviral research · 2023Article
- Apolipoprotein H induces sex-specific steatohepatitis and gut dysbiosis during chronic hepatitis B infection.iScience · 2023Article
- Review
- Lnc-AIFM2-1 promotes HBV immune escape by acting as a ceRNA for miR-330-3p to regulate CD244 expression.Frontiers in immunology · 2023Article
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocyte proliferation could result in the loss of covalently closed circular DNA (cccDNA) and the emergence of cccDNA-cleared nascent hepatocytes, which appear refractory to hepatitis B virus (HBV) reinfection with unknown mechanism(s). Sodium taurocholate cotransporting polypeptide (NTCP) is the functional receptor for HBV entry. In this study, down-regulation of cell membrane localized NTCP expression in proliferating hepatocytes was found to prevent HBV infection in HepG2-NTCP-tet cells and in liver-humanized mice. In patients, lower NTCP protein expression was correlated well with higher levels of hepatocyte proliferation and less HBsAg expression in HBV-related focal nodular hyperplasia (FNH) tissues. Clinically, significantly lower NTCP protein expression was correlated with more active hepatocyte proliferation in CHB patients with severe active necroinflammation and better antiviral treatment outcome. Mechanistically, the activation of cell cycle regulatory genes p53, S-phase kinase-associated protein 2 (SKP2) and cyclin D1 during cell proliferation, as well as proliferative and inflammatory cytokine Interleukin-6 (IL-6) could transcriptionally down-regulate NTCP expression. From these aspects, we conclude that within the milieu of hepatocyte proliferation, down-regulation of cell membrane localized NTCP expression level renders nascent hepatocytes resistant to HBV reinfection. This may accelerate virus clearance during immune-mediated cell death and compensatory proliferation of survival hepatocytes.
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