The Intrinsic Innate Immunity of Hepatocytes Suppresses HBV Replication and Is Antagonized by HBx.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41472269", "kind": "science-record", "revision": 3, "content_hash": "sha256:5a120b2899d29f9caf28e7454748779423957ac784d0b7cd8cf105422b3de162", "created_at": "2026-11-01T20:31:27Z", "updated_at": "2026-11-01T22:15:14Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "The Intrinsic Innate Immunity of Hepatocytes Suppresses HBV Replication and Is Antagonized by HBx.", "doi": "10.3390/v17121599", "pmid": "41472269", "authors": ["Chui Zeng", "Fayed Attia Koutb Megahed", "Yiqiong Guo", "Dongmei Sun", "Yaru Wang", "Qin Liu", "Yanwei Bi", "Jinghang Li", "Qi Zhou", "Qingdong Xie", "Pingnan Sun", "Xiaoling Zhou"], "journal": "Viruses", "year": 2025, "abstract": "(1) Background: Hepatitis B virus (HBV) belongs to the Hepadnaviridae family of viruses that interact with hepatocytes. HBV infection is a major global health problem. Most adults clear the infection quickly after being infected with HBV, while a few people develop chronic HBV infection. It is well-known that the early innate immune response of host cells plays an important role in the fight against virus infection. However, the interactions between HBV and the intrinsic innate immune system of hepatocytes are still not fully understood. The aim of this study was to confirm the interaction between HBV and hepatocytes, and to identify the interferon-stimulated genes (ISGs) regulated by HBx and their expression in association with HBV-associated HCC (HBV-HCC), so that we can refine our understanding of the interaction between HBV and ISGs and its potential influence on HBV-HCC. (2) Methods: We analyzed data concerning the stimulation of IFN-dependent genes in primary human hepatocytes (PHHs) transfected with pathogen DNA mimetics or infected with HBV in the GSE69590 database. Bioinformatic methods, such as GSEA, GO, and KEGG, were used to analyze the differentially expressed innate immunity genes and their related pathways to identify candidate intrinsic innate immune factors. qPCR on HepG2 and Huh7 cells, which highly express HBx, was used to detect relevant intrinsic innate immune factors. qPCR, RNAi, and Elisa methods were used to identify intrinsic innate immune factors in HBV-integrated HepG2.2.15 cells, and bioinformatics analysis was conducted on the HBV-infected tissues and cells in the GEO database. (3) Results: Inhibition of the JAK-STAT pathway enhanced HBV replication in HepG2 cells transfected with HBV plasmid and HepG2-NTCP cells infected with HBV. GSEA analysis of the GSE69590 data revealed significant changes in intrinsic innate immune pathways during HBV infection with PHH for 40 h. A total of 84 differentially expressed, candidate innate immunity genes were identified in GSE69590. Validation showed that TRIM22 and TRIM56 were down-regulated when HBx was expressed. Consistently, TRIM22 and TRIM56 were up-regulated following inhibition of HBx by transfection of HBx siRNA into HepG2.2.15 cells, and HBV pgRNA was up-regulated following down-regulated expression of TRIM22 and TRIM56 in HEK293 cells. Receiver operating characteristics (ROC) and overall survival (OS) analysis of 204 HBV-HCC patients showed that expression of TRIM22 was closely associated with HBV-HCC, and high expression of TRIM22 was associated with longer survival. (4) Conclusions: Innate immunity genes TRIM22 and TRIM56 are regulated by HBx, and higher expression of TRIM22 is closely related to longer survival of HBV-HCC patients.", "claims": [{"id": "claim-method", "statement": "GSE14520 survival data were downloaded from the GEO database, and survival data from HBV-related HCC clinical samples were selected to find the optimal survival cut-off value using X-tile 3.6.1 software [41]. Overall survival analysis and ROC analysis were performed using MedCalc Statistical Software version 20.100 (MedCalc Software Ltd., Ostend, Belgium; https://www.medcalc.org; 2022).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41472269", "locator": "sections[2] \"2. Materials and Methods\" paragraph 8", "quote": "GSE14520 survival data were downloaded from the GEO database, and survival data from HBV-related HCC clinical samples were selected to find the optimal survival cut-off value using X-tile 3.6.1 software [41]. Overall survival analysis and ROC analysis were performed using MedCalc Statistical Software version 20.100 (MedCalc Software Ltd., Ostend, Belgium; https://www.medcalc.org; 2022)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data Availability StatementThe original contributions presented in this study are included in the article. Further inquiries can be directed to the corresponding authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41472269", "locator": "sections[17] \"notes\" paragraph 1", "quote": "Data Availability StatementThe original contributions presented in this study are included in the article. Further inquiries can be directed to the corresponding authors."}], "state": "complete"}, {"id": "claim-target-result", "statement": "High TRIM22 expression was associated with longer overall survival in HBV-associated HCC and distinguished HCC from non-HCC with an AUC of 0.852.", "kind": "quantitative", "target": {"value": 0.852, "unit": "auc", "tolerance": null, "source": "Figure 6 shows that the OS in the high-expression group was higher than in the low-expression group (p = 0.0007), and receiver operating characteristic (ROC) analysis showed an area under the operating characteristics (AUC= 0.852, p < 0.001), indicating that TRIM22 is highly expressed in HBV-associated HCC when patients had a high survival rate."}, "evidence": [{"asset": "source:pmid:41472269", "locator": "sections[9] \"3.6. Expression of TRIM22 and TRIM56 in the Tissues and Cells of HBV-Related HCC Patients\" paragraph 3", "quote": "Figure 6 shows that the OS in the high-expression group was higher than in the low-expression group (p = 0.0007), and receiver operating characteristic (ROC) analysis showed an area under the operating characteristics (AUC= 0.852, p < 0.001), indicating that TRIM22 is highly expressed in HBV-associated HCC when patients had a high survival rate."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "High TRIM22 expression was associated with longer overall survival in HBV-associated HCC and distinguished HCC from non-HCC with an AUC of 0.852.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:41472269"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE14520"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE14520"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:41472269", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3390/v17121599", "sha256": "sha256:b8afcd27c017d230d8935a5be7d77d9384b8a3c4210b731e6b55bc76886feb14", "bytes": 38683, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3390/v17121599", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12737693", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE14520", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE14520", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE14520", "version": null, "note": "Data Availability StatementThe original contributions presented in this study are included in the article. Further inquiries can be directed to the corresponding authors.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Data Availability StatementThe original contributions presented in this study are included in the article. 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