{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T22:32:17Z","timestamp":1791844337508,"version":"4.3.4"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013709","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000}}],"reference-count":74,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T00:00:00Z","timestamp":1765238400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82394464 (82394460)"],"award-info":[{"award-number":["82394464 (82394460)"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81803592"],"award-info":[{"award-number":["81803592"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019018","name":"CAMS Initiative for Innovative Medicine","doi-asserted-by":"crossref","award":["2021-I2M-1-030"],"award-info":[{"award-number":["2021-I2M-1-030"]}],"id":[{"id":"10.13039\/501100019018","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Activation of antiviral immune responses against hepatitis B virus (HBV) is essential for the durable control of chronic HBV infection and the functional cure of chronic hepatitis B. As a molecular hub at the interface of innate and adaptive immunity, the stimulator of interferon (IFN) genes (STING) is well suited as a therapeutic target to break the immune tolerance against chronic viral infections and tumors. Using STING knockout and human STING knock-in mouse models, we first demonstrated that STING agonist treatment activated robust innate immune responses in the spleen and liver and efficiently suppressed HBV DNA replication in the livers of AAV-HBV transduced mice in a STING-dependent manner. We further demonstrate that AAV-HBV transduced mice are well tolerated for the long-term treatment of STING agonist diamidobenzimidazole (diABZI) at the optimized dose and dosing schedules. Virological and hepatic bulk and single-cell RNA-seq analyses revealed that diABZI treatment activated immune responses in liver microenvironment and significantly inhibited HBV replication and HBeAg expression. Antibodies against HBV surface antigen (HBsAg), HBs-Ab, became detectable in 1\/4 mice after 5 weeks of treatment. In conclusion, our findings imply that diABZI treatment activates a STING-dependent immune response that controls HBV replication in a mouse model of persistent HBV infection and thus establishes a scientific basis for further development of STING agonists as immune therapeutics for the treatment of chronic hepatitis B.<\/jats:p>","DOI":"10.1371\/journal.ppat.1013709","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T18:36:49Z","timestamp":1765305409000},"page":"e1013709","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Antiviral and immune modulatory activities of STING agonists in a mouse model of persistent hepatitis B virus infection"],"prefix":"10.1371","volume":"21","author":[{"given":"Ya","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingqiong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijun","family":"Qiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiqiang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ge","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Dong","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3725-3258","authenticated-orcid":true,"given":"Yuhuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,12,9]]},"reference":[{"key":"ppat.1013709.ref001","unstructured":"WHO. 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