{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T00:09:56Z","timestamp":1747181396300,"version":"3.40.5"},"reference-count":33,"publisher":"Microbiology Society","issue":"7","funder":[{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"crossref","award":["18ZR1427300"],"award-info":[{"award-number":["18ZR1427300"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100013103","name":"Shanghai General Hospital","doi-asserted-by":"crossref","award":["02.06.01.20.01"],"award-info":[{"award-number":["02.06.01.20.01"]}],"id":[{"id":"10.13039\/501100013103","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100013076","name":"National Major Science and Technology Projects of China","doi-asserted-by":"crossref","award":["2017ZX10202203-007-005"],"award-info":[{"award-number":["2017ZX10202203-007-005"]}],"id":[{"id":"10.13039\/501100013076","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,7,22]]},"abstract":"<jats:p>Hepatitis B virus surface antigen (HBsAg) encoded by the S gene is highly expressed during the replication cycle of hepatitis B virus (HBV). However, the frequent usage of tryptophan in HBsAg, which leads to a high cost of biosynthesis, is inconsistent with the high expression level of this protein. Tryptophan-truncated mutation of HBsAg, that is, a tryptophan to stop codon mutation resulting in truncated HBsAg, might help to maintain its high expression with lower biosynthetic cost. We aimed to investigate the prevalence of tryptophan-truncated S quasispecies in treatment-na\u00efve patients with chronic hepatitis B (CHB) by applying CirSeq as well as a site-by-site algorithm developed by us to identify variants at extremely low frequencies in the carboxyl terminus of HBsAg. A total of 730 mutations were identified in 27\u2009patients with CHB, varying from seven to 56 mutations per sample. The number of synonymous mutations was much higher than that of nonsynonymous mutations in the reverse transcriptase (RT) coding region and vice versa in the S coding region, implying that the evolutionary constraints on the RT and S genes might be different. We showed that 25 (92.6\u200a%) of 27\u2009patients had at least one S-truncated mutation, most of which were derived from tryptophan, indicating a high prevalence of tryptophan-truncated S mutations in treatment-na\u00efve patients with CHB. In terms of the RT gene, 21 (77.8\u200a%) patients had pre-existing drug-resistant mutations, while no truncated mutations were detected. Our findings that tryptophan-truncated S quasispecies and drug-resistant RT mutants were highly prevalent in treatment-na\u00efve patients with CHB provide new insights into the composition of the HBV population, which might help optimize the treatment and management of patients with CHB.<\/jats:p>","DOI":"10.1099\/jgv.0.001623","type":"journal-article","created":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T17:15:37Z","timestamp":1626974137000},"source":"Crossref","is-referenced-by-count":1,"title":["High prevalence of tryptophan-truncated S quasispecies in treatment-na\u00efve chronic hepatitis B patients"],"prefix":"10.1099","volume":"102","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7260-5277","authenticated-orcid":false,"given":"Hui","family":"Dong","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, PR 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