Oncostatin M Induces IFITM1 Expression to Inhibit Hepatitis B Virus Replication Via JAK-STAT Signaling.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37879404", "kind": "science-record", "revision": 5, "content_hash": "sha256:59c95ba67d9eceaf9f17835c611a6c394a41b97e11b7c5d1896a8058a8e8ef7e", "created_at": "2026-11-01T19:02:44Z", "updated_at": "2026-11-01T22:52:56Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Oncostatin M Induces IFITM1 Expression to Inhibit Hepatitis B Virus Replication Via JAK-STAT Signaling.", "doi": "10.1016/j.jcmgh.2023.10.003", "pmid": "37879404", "authors": ["Yuchen Ye", "Ya Fu", "Caorui Lin", "Ye Shen", "Qingqing Yu", "Xiaobao Yao", "Qunfang Huang", "Can Liu", "Yongbin Zeng", "Tianbin Chen", "Songhang Wu", "Zhen Xun", "Qishui Ou"], "journal": "Cellular and molecular gastroenterology and hepatology", "year": 2024, "abstract": "BACKGROUND & AIMS: Functional cure is achieved by a limited number of patients with chronic hepatitis B (CHB) after nucleotide analogue(s) and interferon treatment. It is urgent to develop therapies that can help a larger proportion of patients achieve functional cure. The present study was designed to explore the anti-hepatitis B virus (HBV) potency of interleukin-6 family cytokines and to characterize the underlying mechanisms of the cytokine displaying the highest anti-HBV potency.\nMETHODS: HBV-infected cells were used to screened the anti-HBV potency of interleukin-6 family cytokines. The concentration of oncostatin M (OSM) in patients with chronic HBV infection was examined by enzyme-linked immunosorbent assay. The underlying mechanism of OSM anti-HBV was explored through RNA-seq. C57BL/6 mice injected with rAAV8-1.3HBV were used to explore the suppression effect of OSM on HBV in vivo.\nRESULTS: OSM is the most effective of the interleukin-6 family cytokines for suppression of HBV replication (percentage of average inhibition: hepatitis B surface antigen, 34.44%; hepatitis B e antigen, 32.52%; HBV DNA, 61.57%). Hepatitis B e antigen-positive CHB patients with high OSM levels had lower hepatitis B surface antigen and hepatitis B e antigen than those with low levels. OSM activated JAK-STAT signaling pathway promoting the formation of STAT1-IRF9 transcription factor complex. Following this, OSM increased the expression of various genes with known functions in innate and adaptive immunity, which was higher expression in patients with CHB in immune clearance phase than in immune tolerance phase (data from GEO: GSE65359). Interferon-induced transmembrane protein 1, one of the most differentially expressed genes, was identified as an HBV restriction factor involved in OSM-mediated anti-HBV effect. In vivo, we also found OSM significantly inhibited HBV replication and induced expression of antiviral effector interferon-induced transmembrane protein 1.\nCONCLUSIONS: Our study shows that OSM remodels the immune response against HBV and exerts potent anti-HBV activity, supporting its further development as a potential therapy for treating CHB.", "claims": [{"id": "claim-method", "statement": "Statistical significance was determined using Student unpaired 2-tailed t test, 1-way analysis of variance, Mann-Whitney test, or Kruskal-Wallis test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37879404", "locator": "sections[23] \"Statistical Analysis\" paragraph 2", "quote": "Statistical significance was determined using Student unpaired 2-tailed t test, 1-way analysis of variance, Mann-Whitney test, or Kruskal-Wallis test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "To evaluate the potential anti-HBV functional roles of these differentially expressed genes, we also analyzed a published dataset from human liver biopsy (GEO: GSE65359) and found that a lot of these genes were higher expression in patients with CHB in immune clearance phase than in immune tolerance phase (Figure 4A).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37879404", "locator": "sections[9] \"OSM Remodels the Immune Response Against HBV of Hepatocytes\" paragraph 2", "quote": "To evaluate the potential anti-HBV functional roles of these differentially expressed genes, we also analyzed a published dataset from human liver biopsy (GEO: GSE65359) and found that a lot of these genes were higher expression in patients with CHB in immune clearance phase than in immune tolerance phase (Figure 4A)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "OSM is the most effective of the interleukin-6 family cytokines for suppression of HBV replication, with average inhibition of 34.44% for HBsAg, 32.52% for HBeAg, and 61.57% for HBV DNA.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37879404", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "OSM is the most effective of the interleukin-6 family cytokines for suppression of HBV replication (percentage of average inhibition: hepatitis B surface antigen, 34.44%; hepatitis B e antigen, 32.52%; HBV DNA, 61.57%)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "OSM is the most effective of the interleukin-6 family cytokines for suppression of HBV replication, with average inhibition of 34.44% for HBsAg, 32.52% for HBeAg, and 61.57% for HBV DNA.", "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:37879404"], "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. 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The underlying mechanism of OSM anti-HBV wa", "concentration of serum OSM was quantified by enzyme-linked immunosorbent assay (R&D Systems, Minneapolis, MN) according to"], "order_basis": "paper_text_order:750", "id": "assay:1"}, {"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["chanism of OSM anti-HBV was explored through RNA-seq. C57BL/6 mice injected with rAAV8-1.3HBV wer"], "order_basis": "paper_text_order:847", "id": "assay:2"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["explore the suppression effect of OSM on HBV in vivo. RESULTS: OSM is the most effective of the i", "or involved in OSM-mediated anti-HBV effect. In vivo, we also found OSM significantly inhibited H"], "order_basis": "paper_text_order:954", "id": "assay:3"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["G2.2.15, HepAD38, Huh7, and HepG2 cells were cultured in Dulbecco’s modified Eagle medium (Meilunbio,", "he manufacturer’s instructions. Cell Culture HepG2.2.15, HepAD38, Huh7, and HepG2 cells were cu", "Cell Culture HepG2.2.15, HepAD38, Huh7, and HepG2 cells were cultured in Dulbecco’s modified E", "ced at 37°C in 5% CO2 humidified incubators. HepG2.2.15 and HepAD38 stably expresses HBV genome"], "order_basis": "paper_text_order:3114", "id": "assay:4"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["stably expresses HBV genome. Huh7 cells were transfected with HBV 1.3-mer wild-type replicon (QCHENG", "replicon (QCHENG BIO, Shanghai, China) using transfection reagent FuGENE HD (Promega, Fitchburg, WI) t", "HD (Promega, Fitchburg, WI) to generate HBV transfection–based cell culture Huh7-1.3. 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