{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T16:00:35Z","timestamp":1792425635980,"version":"4.5.0"},"reference-count":166,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Innate immunity constrains the hepatitis B virus (HBV) by sensing pathogen-associated molecular patterns (PAMPs) and inducing type I\/III interferons and interferon-stimulated genes. This review synthesizes molecular mechanisms by which HBV nucleic acids and proteins are detected by pattern recognition receptors (PRRs) and how the virus evades such surveillance. At the DNA level, covalently closed circular DNA (cccDNA) persists as a chromatin-like episome with low immunogenicity; cGAS\u2013STING signaling is functionally dampened, whereas nuclear interferon-inducible protein 16(IFI16) and cytoplasmic\/nuclear ABCF1 bind cccDNA to repress transcription, and APOBEC3A-mediated deamination requires robust interferon signaling. At the RNA level, TLR3\/7\/8 and retinoic acid-inducible Gene I(RIG-I) sense circulating HBV RNA and 5\u2032-triphosphate pregenomic RNA, respectively. HBV counteracts RIG-I-like receptor (RLR) pathways through ADAR1 editing, TIAR-dependent translational control, and a metabolic checkpoint involving lactate-MAVS\/hexokinase, whereas spliced viral RNAs (svRNAs) have emerged as immunologically relevant species. At the protein level, Hepatitis B Surface Antigen (HBsAg) impairs interferons (IFN) induction by blocking the TAK1\u2013TAB2\u2013NF-\u03baB\/IRF axis; Hepatitis B Virus X Protein (HBx) sustains cccDNA transcription via DDB1-directed Smc5\/6 degradation and broadly suppresses PRR\/IFN signaling, with TRIM25 acting as a host restriction factor. These insights nominate combinatorial strategies\u2014PRR agonists (TLR\/STING), MAVS sensitization, metabolic disinhibition, pharmacological disruption of the HBx\u2013DDB1 axis, and reinforcement of IFI16\/ABCF1\u2014to achieve functional control of cccDNA and advance curative hepatitis B virus (HBV) therapy.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1741620","type":"journal-article","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T06:47:42Z","timestamp":1772520462000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Innate immune recognition and evasion strategies of hepatitis B virus: from DNA to RNA and viral proteins"],"prefix":"10.3389","volume":"17","author":[{"given":"Zhenghao","family":"Chen","sequence":"first","affiliation":[{"name":"Alberta Institute, Wenzhou Medical University","place":["Wenzhou, China"]},{"name":"Department of Gastroenterology and Hepatology, The First Affiliated Hospital of 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