{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T07:03:25Z","timestamp":1777100605771,"version":"3.51.4"},"reference-count":63,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,1,12]],"date-time":"2021-01-12T00:00:00Z","timestamp":1610409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017001","name":"Li Ka Shing Institute of Virology, University of Alberta","doi-asserted-by":"publisher","award":["none"],"award-info":[{"award-number":["none"]}],"id":[{"id":"10.13039\/501100017001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009192","name":"Alberta Innovates","doi-asserted-by":"publisher","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}],"id":[{"id":"10.13039\/501100009192","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>An estimated two billion people worldwide have been infected with hepatitis B virus (HBV). Despite the high infectivity of HBV in vivo, a lack of easily infectable in vitro culture systems hinders studies of HBV. Overexpression of the sodium taurocholate co-transporting polypeptide (NTCP) bile acid transporter in hepatoma cells improved infection efficiency. We report here a hepatoma cell culture system that does not require dimethyl sulfoxide (DMSO) for HBV infection. We overexpressed NTCP in Huh7.5 cells and allowed these cells to differentiate in a medium supplemented with human serum (HS) instead of fetal bovine serum (FBS). We show that human serum culture enhanced HBV infection in Huh7.5-NTCP cells, e.g., in HS cultures, HBV pgRNA levels were increased by as much as 200-fold in comparison with FBS cultures and 19-fold in comparison with FBS+DMSO cultures. Human serum culture increased levels of hepatocyte differentiation markers, such as albumin secretion, in Huh7.5-NTCP cells to similar levels found in primary human hepatocytes. N-glycosylation of NTCP induced by culture in human serum may contribute to viral entry. Our study demonstrates an in vitro HBV infection of Huh7.5-NTCP cells without the use of potentially toxic DMSO.<\/jats:p>","DOI":"10.3390\/v13010097","type":"journal-article","created":{"date-parts":[[2021,1,12]],"date-time":"2021-01-12T20:11:31Z","timestamp":1610482291000},"page":"97","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["In Vitro Infection with Hepatitis B Virus Using Differentiated Human Serum Culture of Huh7.5-NTCP Cells without Requiring Dimethyl Sulfoxide"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4864-7420","authenticated-orcid":false,"given":"Connie","family":"Le","sequence":"first","affiliation":[{"name":"Li Ka Shing Institute of Virology, Department of Medical Microbiology and Immunology, 6010 Katz Centre for Health Research, University of Alberta, Edmonton, AB T6G 2E1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3460-6153","authenticated-orcid":false,"given":"Reshma","family":"Sirajee","sequence":"additional","affiliation":[{"name":"Li Ka Shing Institute of Virology, Department of Medical Microbiology and Immunology, 6010 Katz Centre for Health Research, University of Alberta, Edmonton, AB T6G 2E1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7399-9335","authenticated-orcid":false,"given":"Rineke","family":"Steenbergen","sequence":"additional","affiliation":[{"name":"Li Ka Shing Institute of Virology, Department of Medical Microbiology and Immunology, 6010 Katz Centre for Health Research, University of Alberta, Edmonton, AB T6G 2E1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9173-7299","authenticated-orcid":false,"given":"Michael A.","family":"Joyce","sequence":"additional","affiliation":[{"name":"Li Ka Shing Institute of Virology, Department of Medical Microbiology and Immunology, 6010 Katz Centre for Health Research, University of Alberta, Edmonton, AB T6G 2E1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William R.","family":"Addison","sequence":"additional","affiliation":[{"name":"Li Ka Shing Institute of Virology, Department of Medical Microbiology and Immunology, 6010 Katz Centre for Health Research, University of Alberta, Edmonton, AB T6G 2E1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0983-7267","authenticated-orcid":false,"given":"D. Lorne","family":"Tyrrell","sequence":"additional","affiliation":[{"name":"Li Ka Shing Institute of Virology, Department of Medical Microbiology and Immunology, 6010 Katz Centre for Health Research, University of Alberta, Edmonton, AB T6G 2E1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.1016\/j.vaccine.2011.12.116","article-title":"Global epidemiology of hepatitis B virus infection: New estimates of age-specific HBsAg seroprevalence and endemicity","volume":"30","author":"Ott","year":"2012","journal-title":"Vaccine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1546","DOI":"10.1016\/S0140-6736(15)61412-X","article-title":"Estimations of worldwide prevalence of chronic hepatitis B virus infection: A systematic review of data published between 1965 and 2013","volume":"386","author":"Schweitzer","year":"2015","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/S2468-1253(18)30056-6","article-title":"Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: A modelling study","volume":"3","author":"Gamkrelidze","year":"2018","journal-title":"Lancet Gastroenterol. 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