{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T01:43:39Z","timestamp":1782956619710,"version":"3.54.5"},"reference-count":185,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:00:00Z","timestamp":1760054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"crossref","award":["2022YFA1303600"],"award-info":[{"award-number":["2022YFA1303600"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"crossref","award":["2024YFC2311000"],"award-info":[{"award-number":["2024YFC2311000"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["U23A20474"],"award-info":[{"award-number":["U23A20474"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82372234"],"award-info":[{"award-number":["82372234"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["M-0060"],"award-info":[{"award-number":["M-0060"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Chronic hepatitis B (CHB) remains a major global health challenge, largely due to the persistence of covalently closed circular DNA (cccDNA) and impaired host immunity. Interferon-\u03b1 (IFN-\u03b1), a key antiviral cytokine, not only directly restricts HBV replication but also orchestrates innate and adaptive immune responses. This review summarizes current advances in IFN-\u03b1-mediated immune regulation, highlighting its effects across diverse immune cell populations. Evidence indicates that IFN-\u03b1 can reprogram immune responses to promote viral clearance, although clinical efficacy is limited by modest response rates and adverse effects. Recent progress in cytokine engineering, subtype research, and rational combination strategies\u2014including nucleo(s\/t)ide analogs, RNA interference therapeutics, antisense oligonucleotides, therapeutic vaccines, and beyond\u2014has expanded opportunities to improve treatment outcomes. While challenges remain, these advances lay the foundation for optimizing IFN-\u03b1\u2013based interventions and highlight IFN-\u03b1 as a key driver for innovative therapies aimed at achieving a functional cure of chronic hepatitis B.<\/jats:p>","DOI":"10.3390\/v17101358","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:50:16Z","timestamp":1760107816000},"page":"1358","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Interferon-\u03b1 for Immune Modulation in Chronic Hepatitis B Toward Functional Cure"],"prefix":"10.3390","volume":"17","author":[{"given":"Asha","family":"Ashuo","sequence":"first","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology (MOE\/NHC), Research Unit of Cure of Chronic Hepatitis B Virus Infection (CAMS), Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, School of Basic Medical Sciences, Shanghai Medical College Fudan University, Shanghai, 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenghong","family":"Yuan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology (MOE\/NHC), Research Unit of Cure of Chronic Hepatitis B Virus Infection (CAMS), Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, School of Basic Medical Sciences, Shanghai Medical College Fudan University, Shanghai, 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9647-0239","authenticated-orcid":false,"given":"Jieliang","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology (MOE\/NHC), Research Unit of Cure of Chronic Hepatitis B Virus Infection (CAMS), Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, School of Basic Medical Sciences, Shanghai Medical College Fudan University, Shanghai, 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s41577-021-00549-4","article-title":"Immunobiology and pathogenesis of hepatitis B virus infection","volume":"22","author":"Iannacone","year":"2021","journal-title":"Nat. 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