{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T21:42:12Z","timestamp":1791582132293,"version":"4.3.4"},"reference-count":56,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2022,8,4]],"date-time":"2022-08-04T00:00:00Z","timestamp":1659571200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005564","name":"Gilead Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005564","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Chronic hepatitis B virus (HBV) infection is characterized by the presence of high circulating levels of non-infectious lipoprotein-like HBV surface antigen (HBsAg) particles thought to contribute to chronic immune dysfunction in patients. Lipid and metabolomic analysis of humanized livers from immunodeficient chimeric mice (uPA\/SCID) revealed that HBV infection dysregulates several lipid metabolic pathways. Small molecule inhibitors of lipid biosynthetic pathway enzymes acetyl-CoA carboxylase (ACC), fatty acid synthase, and subtilisin kexin isozyme-1\/site-1 protease in HBV-infected HepG2-NTCP cells demonstrated potent and selective reduction of extracellular HBsAg. However, a liver-targeted ACC inhibitor did not show antiviral activity in HBV-infected liver chimeric mice, despite evidence of on-target engagement. Our study suggests that while HBsAg production may be dependent on hepatic de novo lipogenesis <jats:italic>in vitro<\/jats:italic>, this may be overcome by extrahepatic sources (such as lipolysis or diet) <jats:italic>in vivo<\/jats:italic>. Thus, a combination of agents targeting more than one lipid metabolic pathway may be necessary to reduce HBsAg levels in patients with chronic HBV infection.<\/jats:p>","DOI":"10.1371\/journal.pone.0270273","type":"journal-article","created":{"date-parts":[[2022,8,4]],"date-time":"2022-08-04T17:36:40Z","timestamp":1659634600000},"page":"e0270273","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":21,"title":["Targeting lipid biosynthesis pathways for hepatitis B virus cure"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0412-6404","authenticated-orcid":true,"given":"Anastasia","family":"Hyrina","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dara","family":"Burdette","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijuan","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Ramirez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayse","family":"Okesli-Armlovich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Archana","family":"Vijayakumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie","family":"Bates","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James L.","family":"Trevaskis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon P.","family":"Fletcher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William A.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan M.","family":"Holdorf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,8,4]]},"reference":[{"key":"pone.0270273.ref001","volume-title":"Global hepatitis report, 2017.","author":"WHO","year":"2017"},{"issue":"10","key":"pone.0270273.ref002","doi-asserted-by":"crossref","first-page":"4588","DOI":"10.1172\/JCI121960","article-title":"Circulating and intrahepatic antiviral B cells are defective in hepatitis B","volume":"128","author":"AR Burton","year":"2018","journal-title":"J Clin Invest"},{"issue":"10","key":"pone.0270273.ref003","doi-asserted-by":"crossref","first-page":"4573","DOI":"10.1172\/JCI121957","article-title":"PD-1 blockade partially recovers dysfunctional virus-specific B cells in chronic hepatitis B infection","volume":"128","author":"L Salimzadeh","year":"2018","journal-title":"J Clin Invest"},{"issue":"1","key":"pone.0270273.ref004","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.jhep.2019.07.015","article-title":"Comparative characterization of B cells specific for HBV nucleocapsid and envelope proteins in patients with chronic hepatitis B","volume":"72","author":"N Le Bert","year":"2020","journal-title":"J Hepatol"},{"issue":"6","key":"pone.0270273.ref005","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1053\/j.gastro.2020.01.032","article-title":"Knockdown of Virus Antigen Expression Increases Therapeutic Vaccine Efficacy in High-Titer Hepatitis B Virus Carrier Mice","volume":"158","author":"T Michler","year":"2020","journal-title":"Gastroenterology"},{"issue":"12","key":"pone.0270273.ref006","doi-asserted-by":"crossref","first-page":"1972","DOI":"10.1136\/gutjnl-2015-309809","article-title":"HBV cccDNA: viral persistence reservoir and key obstacle for a cure of chronic hepatitis B","volume":"64","author":"M. 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