{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:36:10Z","timestamp":1790753770468,"version":"4.1.0"},"reference-count":117,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,11,6]],"date-time":"2020-11-06T00:00:00Z","timestamp":1604620800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI110762, R01AI123271, R01AI134818, R01AI150255, and T32AI060519."],"award-info":[{"award-number":["R01AI110762, R01AI123271, R01AI134818, R01AI150255, and T32AI060519."]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The chronic factor of the Hepatitis B Virus (HBV), specifically the covalently closed circular DNA (cccDNA), is a highly stable and active viral episomal genome established in the livers of chronic hepatitis B patients as a constant source of disease. Being able to target and eliminate cccDNA is the end goal for a genuine cure for HBV. Yet how HBV cccDNA is formed from the viral genomic relaxed circular DNA (rcDNA) and by what host factors had been long-standing research questions. It is generally acknowledged that HBV hijacks cellular functions to turn the open circular DNA conformation of rcDNA into cccDNA through DNA repair mechanisms. With great efforts from the HBV research community, there have been several recent leaps in our understanding of cccDNA formation. It is our goal in this review to analyze the recent reports showing evidence of cellular factor\u2019s involvement in the molecular pathway of cccDNA biosynthesis.<\/jats:p>","DOI":"10.3390\/cells9112430","type":"journal-article","created":{"date-parts":[[2020,11,8]],"date-time":"2020-11-08T19:03:37Z","timestamp":1604862217000},"page":"2430","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["New Insights on Molecular Mechanism of Hepatitis B Virus Covalently Closed Circular DNA Formation"],"prefix":"10.3390","volume":"9","author":[{"given":"Alexander L.","family":"Marchetti","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, School of Medicine, Indiana University, Indianapolis, IN 46202, USA"},{"name":"Cancer Virology Program, Hillman Cancer Center, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haitao","family":"Guo","sequence":"additional","affiliation":[{"name":"Cancer Virology Program, Hillman Cancer Center, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA"},{"name":"Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/S2468-1253(19)30119-0","article-title":"A global scientific strategy to cure hepatitis B","volume":"4","author":"Revill","year":"2019","journal-title":"Lancet Gastroenterol. 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