{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:38:30Z","timestamp":1790836710054,"version":"4.1.0"},"reference-count":23,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2020,10,31]],"date-time":"2020-10-31T00:00:00Z","timestamp":1604102400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2020,10,31]],"date-time":"2020-10-31T00:00:00Z","timestamp":1604102400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>An efficient cell\u2010culture system for hepatitis B virus (HBV) is indispensable for research on viral characteristics and antiviral reagents. Currently, for the HBV infection assay in cell culture, viruses derived from HBV genome\u2010integrated cell lines of HepG2.2.15 or HepAD\u201038 are commonly used. However, these viruses are not suitable for the evaluation of polymorphism\u2010dependent viral characteristics or resistant mutations against antiviral reagents. HBV obtained by the transient transfection of the ordinary HBV molecular clone has limited infection efficiencies in cell culture.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>We found that an 11\u2010amino\u2010acid deletion (d11) in the preS1 region enhances the infectivity of cell\u2010culture\u2013generated HBV (HBVcc) to sodium taurocholate cotransporting polypeptide\u2013transduced HepG2 (HepG2\/NTCP) cells. Infection of HBVcc derived from a d11\u2010introduced genotype C strain (GTC\u2010d11) was ~10\u2010fold more efficient than infection of wild\u2010type GTC (GTC\u2010wt), and the number of infected cells was comparable between GTC\u2010d11\u2010 and HepG2.2.15\u2010derived viruses when inoculated with the same genome equivalents. A time\u2010dependent increase in pregenomic RNA and efficient synthesis of covalently closed circular DNA were detected after infection with the GTC\u2010d11 virus. The involvement of d11 in the HBV large surface protein in the enhanced infectivity was confirmed by an HBV reporter virus and hepatitis D virus infection system. The binding step of the GTC\u2010d11 virus onto the cell surface was responsible for this efficient infection.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>This system provides a powerful tool for studying the infection and propagation of HBV in cell culture and also for developing the antiviral strategy against HBV infection.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.31308","type":"journal-article","created":{"date-parts":[[2020,5,23]],"date-time":"2020-05-23T19:00:39Z","timestamp":1590260439000},"page":"520-532","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":29,"title":["N\u2010Terminal PreS1 Sequence Regulates Efficient Infection of Cell\u2010Culture\u2013Generated Hepatitis B Virus"],"prefix":"10.1097","volume":"73","author":[{"given":"Asako","family":"Murayama","sequence":"first","affiliation":[{"name":"Department of Virology II,National Institute of Infectious Diseases,Tokyo,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norie","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Virology II,National Institute of Infectious Diseases,Tokyo,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiki","family":"Osaki","sequence":"additional","affiliation":[{"name":"Department of Virology II,National Institute of Infectious Diseases,Tokyo,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaaki","family":"Shiina","sequence":"additional","affiliation":[{"name":"Department of Virology II,National Institute of Infectious Diseases,Tokyo,Japan"},{"name":"Department of Gastroenterology and Hepatology,Shin\u2010Yurigaoka General Hospital,Kawasaki,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hussein Hassan","family":"Aly","sequence":"additional","affiliation":[{"name":"Department of Virology II,National Institute of Infectious Diseases,Tokyo,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Iwamoto","sequence":"additional","affiliation":[{"name":"Department of Virology II,National Institute of Infectious Diseases,Tokyo,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Senko","family":"Tsukuda","sequence":"additional","affiliation":[{"name":"Department of Virology II,National Institute of Infectious Diseases,Tokyo,Japan"},{"name":"Liver Cancer Prevention Research Unit,Center for Integrative Medical Sciences,RIKEN,Wako,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Watashi","sequence":"additional","affiliation":[{"name":"Department of Virology II,National Institute of Infectious Diseases,Tokyo,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mami","family":"Matsuda","sequence":"additional","affiliation":[{"name":"Department of Virology II,National Institute of Infectious Diseases,Tokyo,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryosuke","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Virology II,National Institute of Infectious Diseases,Tokyo,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohisa","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Microbiology,Graduate School of Medicine,University of Yamanashi,Chuo\u2010shi,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohji","family":"Moriishi","sequence":"additional","affiliation":[{"name":"Department of Microbiology,Graduate School of Medicine,University of Yamanashi,Chuo\u2010shi,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuro","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Virology and Parasitology,Hamamatsu University School of Medicine,Shizuoka,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironori","family":"Nishitsuji","sequence":"additional","affiliation":[{"name":"Genome Medical Sciences Project,National Center for Global Health and Medicine,Ichikawa,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9084-7197","authenticated-orcid":false,"given":"Masaya","family":"Sugiyama","sequence":"additional","affiliation":[{"name":"Genome Medical Sciences Project,National Center for Global Health and Medicine,Ichikawa,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Mizokami","sequence":"additional","affiliation":[{"name":"Genome Medical Sciences Project,National Center for Global Health and Medicine,Ichikawa,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunitada","family":"Shimotohno","sequence":"additional","affiliation":[{"name":"Genome Medical Sciences Project,National 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