{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T18:04:57Z","timestamp":1791309897695,"version":"4.3.1"},"reference-count":28,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antiviral Therapy"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>High genetic variability at the reverse transcriptase (RT) region of HBV could confer resistance to nucleoside\/nucleotide analogues (NUCs). The aim of this study was to identify new RT amino acid (AA) substitutions related to NUC resistance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>HBV RT sequences of genotype C from 501 chronic hepatitis B (CHB) patients were analysed to identify potential RT substitutions related to NUC resistance. In vitro studies without and with NUCs were performed in a HepG2 cell line transfected by clones with RT harbouring wild-type or substituted AA(s) of interest.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 261 NUC-treated CHB patients, we found a high detection rate of rtM204I\/V substitution (30.7% [80\/261]). We identified a new substitution of rtH55R, and its detection rate had a significantly increasing trend from 3.8% (9\/240) in the untreated group to 7.2% (13\/181) or 33.8% (27\/80) in the treated group with rtM204 or with rtM204I\/V substitutions ( P&lt;0.0001). In vitro studies showed that rtH55R had a similar HBV DNA level compared to wild type. The rtH55R+rtM204I clone had a significantly better replication capacity than the rtM204I clone without NUCs ( P&lt;0.05). The replication capacity of the rtM204I clone was found to significantly decrease under lamivudine treatment, but this was not found in the rtH55R+rtM204I clone.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We identified a new HBV RT substitution of rtH55R in genotype-C-infected CHB patients. It is frequently found in combination with rtM204I\/V substitution under NUC treatment. In vitro studies suggest that it might play some replication compensatory role in rtM204I mutants under lamivudine treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3851\/imp3170","type":"journal-article","created":{"date-parts":[[2017,4,25]],"date-time":"2017-04-25T10:34:18Z","timestamp":1493116458000},"page":"33-42","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["Impacts of HBV rtH55R Polymerase Substitution on Viral Replication and rtM204I\/V Resistance to Nucleoside\/Nucleotide Antiviral Drugs"],"prefix":"10.1177","volume":"23","author":[{"given":"Kuan-Hui","family":"Xiang","sequence":"first","affiliation":[{"name":"Department of Microbiology and Center of Infectious Disease, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Yu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Center of Infectious Disease, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Center of Infectious Disease, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Center of Infectious Disease, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Ze","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Center of Infectious Disease, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang-Yi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Center of Infectious Disease, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi-Zhan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Center of Infectious Disease, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Center of Infectious Disease, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Center of Infectious Disease, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Center of Infectious Disease, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 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