{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T22:20:56Z","timestamp":1772490056405,"version":"3.50.1"},"reference-count":60,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T00:00:00Z","timestamp":1764201600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T00:00:00Z","timestamp":1764201600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["MicrobiologyOpen"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The evolutionary profile of hepatitis B virus (HBV) quasispecies may influence the clinical course of chronic hepatitis B (CHB), but few studies have characterized quasispecies according to hepatitis B e antigen (HBeAg) status. In this study, we analyzed 289 full\u2010length HBV clones from 19 treatment\u2010na\u00efve CHB patients with long\u2010term infection (&gt;\u200910 years), comprising nine HBeAg\u2010positive and ten HBeAg\u2010negative, using molecular cloning and Sanger sequencing. Compared with HBeAg\u2010positive patients, HBeAg\u2010negative patients displayed higher quasispecies diversity (mean intrapatient sequence divergence 1.09% vs. 0.44%) and more complex phylogenetic structures. They also exhibited a greater number of positively selected sites, with 70.8% located within known\n                    <jats:italic>T<\/jats:italic>\n                    \u2010 or\n                    <jats:italic>B<\/jats:italic>\n                    \u2010cell epitope regions, predominantly in the surface (S), polymerase (Pol), and\n                    <jats:italic>X<\/jats:italic>\n                    regions. Classical basal core promoter (BCP) and precore (PreC) mutations were detected in 52.8% of HBeAg\u2010negative clones, often coexisting with wild\u2010type strains. In patients lacking these classical BCP\/preC mutations but showing sustained viremia, intrahost recombination was observed. Moreover, overlapping reading frames, particularly +1 frameshifts in Pol\/S region, demonstrated asymmetric distribution patterns. In patients harboring deletion mutations, intact quasispecies were also maintained. Collectively, these findings reveal multiple adaptive strategies that sustain HBV replication and immune escape in HBeAg\u2010negative patients, providing mechanistic insights for disease monitoring and therapeutic interventions.\n                  <\/jats:p>","DOI":"10.1002\/mbo3.70175","type":"journal-article","created":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T04:44:16Z","timestamp":1764305056000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Adaptive Evolution and Distinct Mutation Signatures of Full\u2010Length HBV Quasispecies in HBeAg\u2010Negative Chronic Hepatitis B"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-7263-289X","authenticated-orcid":false,"given":"Changhui","family":"Wu","sequence":"first","affiliation":[{"name":"Kunming Medical University Kunming Yunnan China"},{"name":"Department of Infectious Diseases and Hepatology the Affiliated Hospital of Yunnan University Kunming Yunnan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fengwei","family":"Liu","sequence":"additional","affiliation":[{"name":"Kunming Medical University Kunming Yunnan China"},{"name":"Central Laboratory the Affiliated Hospital of Yunnan University Kunming Yunnan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Li","sequence":"additional","affiliation":[{"name":"Central Laboratory the Affiliated Hospital of Yunnan University Kunming Yunnan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaojin","family":"Li","sequence":"additional","affiliation":[{"name":"Central Laboratory the Affiliated Hospital of Yunnan University Kunming Yunnan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Hepatology the Affiliated Hospital of Yunnan University Kunming Yunnan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sihang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Kunming Medical University Kunming Yunnan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaohui","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Hepatology the Affiliated Hospital of Yunnan University Kunming Yunnan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taicheng","family":"Zhou","sequence":"additional","affiliation":[{"name":"Central Laboratory the Affiliated Hospital of Yunnan University Kunming Yunnan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Hepatology the Affiliated Hospital of Yunnan University Kunming Yunnan China"},{"name":"Central Laboratory the Affiliated Hospital of Yunnan University Kunming Yunnan China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,11,27]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i24.7644"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2015-309300"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/v14081691"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-025-10873-9"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0060098"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2021.105184"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-83762-4"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-virology-101416-041718"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1261\/rna.080280.124"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.05023-11"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/v13030473"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-71165-8_15"},{"key":"e_1_2_11_14_1","doi-asserted-by":"crossref","unstructured":"Gu Z. 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