ArticlePLoS pathogens2014
Hepatitis B virus infection and immunopathogenesis in a humanized mouse model: induction of human-specific liver fibrosis and M2-like macrophages.
Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 151 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
151 citing papers in PubMed, 1 synthesis or guideline pooled it, 221 citations in OpenAlex.
- The Role of Paracrine Regulation of Mesenchymal Stem Cells in the Crosstalk With Macrophages in Musculoskeletal Diseases: A Systematic Review.Frontiers in bioengineering and biotechnology · 2020Pooled it
- Review
- Liver Macrophages in the Pathogenesis of Viral Hepatitis.Current issues in molecular biology · 2026Review
- Review
- Immune Exhaustion in Chronic Infection and Cancer: Signaling Pathways and Therapeutic Interventions.MedComm · 2026Review
- JAK3-deficient mini-pigs exhibit impaired lymphoid organogenesis, intestinal structure, and leukocyte/cytokine production.Journal of advanced research · 2026Article
- Functional immune responses induced by a capsid assembly modulator in chronic hepatitis B virus-infected humanized mice.Cell host & microbe · 2026Article
- Strategies to promote liver fibrosis amelioration with involvement of restorative macrophages.Frontiers in immunology · 2026Review
- Review
- Hepatitis B Virus e Antigen in Mother-to-Child Transmission and Clinical Management of Hepatitis B.Viruses · 2025Review
- The role of liver macrophages in viral liver pathogenesis.Journal of leukocyte biology · 2025Review
- MSP-RON signaling in liver pathobiology and as an emerging therapeutic target: a review of the current evidence.Cell communication and signaling : CCS · 2025Review
- Potential role of liver-resident CD3JHEP reports : innovation in hepatology · 2025Article
- Can Humanized Immune System Mouse and Rat Models Accelerate the Development of Cytomegalovirus-Based Vaccines Against Infectious Diseases and Cancers?International journal of molecular sciences · 2025Review
- Developing T Cell Epitope-Based Vaccines Against Infection: Challenging but Worthwhile.Vaccines · 2025Review
- Current Treatment Regimens and Promising Molecular Therapies for Chronic Hepatobiliary Diseases.Biomolecules · 2025Review
- [Immune status of inactive HBsAg antigen carriers with chronic HBV infection].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2024Article
- Mice Engrafted with Human Liver Cells.Seminars in liver disease · 2024Review
- YAP mediates HIV-related liver fibrosis.JHEP reports : innovation in hepatology · 2024Article
- Review
91 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
The mechanisms of chronic HBV infection and immunopathogenesis are poorly understood due to a lack of a robust small animal model. Here we report the development of a humanized mouse model with both human immune system and human liver cells by reconstituting the immunodeficient A2/NSG (NOD.Cg-Prkdc(scid) Il2rg(tm1Wjl)/SzJ mice with human HLA-A2 transgene) with human hematopoietic stem cells and liver progenitor cells (A2/NSG-hu HSC/Hep mice). The A2/NSG-hu HSC/Hep mouse supported HBV infection and approximately 75% of HBV infected mice established persistent infection for at least 4 months. We detected human immune responses, albeit impaired in the liver, chronic liver inflammation and liver fibrosis in infected animals. An HBV neutralizing antibody efficiently inhibited HBV infection and associated liver diseases in humanized mice. In addition, we found that the HBV mediated liver disease was associated with high level of infiltrated human macrophages with M2-like activation phenotype. Importantly, similar M2-like macrophage accumulation was confirmed in chronic hepatitis B patients with liver diseases. Furthermore, gene expression analysis showed that induction of M2-like macrophage in the liver is associated with accelerated liver fibrosis and necrosis in patients with acute HBV-induced liver failure. Lastly, we demonstrate that HBV promotes M2-like activation in both M1 and M2 macrophages in cell culture studies. Our study demonstrates that the A2/NSG-hu HSC/Hep mouse model is valuable in studying HBV infection, human immune responses and associated liver diseases. Furthermore, results from this study suggest a critical role for macrophage polarization in hepatitis B virus-induced immune impairment and liver pathology.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.