2. Academic Validation
  3. Oncostatin M induces IFITM1 expression to inhibit hepatitis B virus replication via JAK-STAT signaling

Oncostatin M induces IFITM1 expression to inhibit hepatitis B virus replication via JAK-STAT signaling

  • Cell Mol Gastroenterol Hepatol. 2023 Oct 23:S2352-345X(23)00182-0. doi: 10.1016/j.jcmgh.2023.10.003.
Yuchen Ye 1,  Ya Fu 2,  Caorui Lin 2,  Ye Shen 3,  Qingqing Yu 3,  Xiaobao Yao 1,  Qunfang Huang 1,  Can Liu 2,  Yongbin Zeng 2,  Tianbin Chen 1,  Songhang Wu 4,  Zhen Xun 5,  Qishui Ou 6
Affiliations

Affiliations

  • 1 Department of Laboratory Medicine, Gene Diagnosis Research Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China; Clinical Laboratory Diagnostics, The First Clinical College, Fujian Medical University, Fuzhou, China.
  • 2 Department of Laboratory Medicine, Gene Diagnosis Research Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China; Fujian Clinical Research Center for Clinical Immunology Laboratory Test, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China; Department of Laboratory Medicine, National Reginal Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
  • 3 Clinical Laboratory Diagnostics, The First Clinical College, Fujian Medical University, Fuzhou, China.
  • 4 Department of Laboratory Medicine, Gene Diagnosis Research Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
  • 5 Department of Laboratory Medicine, Gene Diagnosis Research Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China; Fujian Clinical Research Center for Clinical Immunology Laboratory Test, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China; Department of Laboratory Medicine, National Reginal Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China. Electronic address: [email protected].
  • 6 Department of Laboratory Medicine, Gene Diagnosis Research Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China; Fujian Clinical Research Center for Clinical Immunology Laboratory Test, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China; Department of Laboratory Medicine, National Reginal Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China. Electronic address: [email protected].
PMID: 37879404 DOI: 10.1016/j.jcmgh.2023.10.003
Abstract

Background & aims: Functional cure is achieved by a limited number of chronic hepatitis B (CHB) patients after nucleotide(s) analogues and interferon treatment. It's urgent to develop therapies that can help a larger proportion of patients achieve functional cure. The present study was designed to explore the anti-HBV potency of IL-6 family cytokines and to characterize the underlying mechanisms of the cytokine displaying the highest anti-HBV potency.

Methods: HBV-infected cells were used to screened the anti-HBV potency of IL-6 family cytokines. The concentration of Oncostatin M (OSM) in chronic HBV Infection patients was examined by ELISA. The underlying mechanism of OSM anti-HBV was explored thought RNA-seq. C57BL/6 mice injected with rAAV8-1.3HBV were used to explore the suppression effect of OSM on HBV in vivo.

Results: OSM is the most effective of the IL-6 family cytokines for suppression of HBV replication (percentage of average inhibition: HBsAg 34.44%, HBeAg 32.52%, and HBV DNA 61.57%). HBeAg-positive CHB patients with high OSM levels had lower HBsAg and HBeAg 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 CHB patients in immune clearance phase than in immune tolerance phase (data from: GEO: GSE65359). Interferon-induced transmembrane protein 1 (IFITM1), 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 IFITM1.

Conclusions: 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.

Keywords

Hepatitis B virus; Interferon induced transmembrane protein 1; Interleukin-6 family cytokines; JAK-STAT signaling; Oncostatin M.

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