https://scholars.lib.ntu.edu.tw/handle/123456789/568507
標題: | Influence of mutations in hepatitis B virus surface protein on viral antigenicity and phenotype in occult HBV strains from blood donors | 作者: | Huang C.-H. Yuan Q. PEI-JER CHEN Zhang Y.-L. Chen C.-R. Zheng Q.-B. Shiou-Hwei Yeh Yu H. Xue Y. Chen Y.-X. Liu P.-G. Ge S.-X. Zhang J. Xia N.-S. |
關鍵字: | Antigenicity; HBsAg mutants; Occult HBV infection; Secretion deficiency | 公開日期: | 2012 | 出版社: | Elsevier | 卷: | 57 | 期: | 4 | 起(迄)頁: | 720-729 | 來源出版物: | Journal of Hepatology | 摘要: | Background & Aims: This study aimed at investigating mutations in the hepatitis B surface protein (HBsAg) in occult hepatitis B virus (HBV) infection (OBI) and their influence on viral antigenicity and phenotype. Methods: The characteristics of 61 carriers with OBI (OBI group), 153 HBsAg(+) carriers with serum HBsAg ?100 IU/ml (HBsAg-L group) and 54 carriers with serum HBsAg >100 IU/ml (HBsAg-H group) from 38,499 blood donors were investigated. Mutations in the major hydrophilic region (MHR) of the viral sequences were determined. Thirteen representative MHR mutations observed in OBI sequences were antigenically characterized with a panel of monoclonal antibodies (MAbs) and commercial HBsAg immunoassays and functionally characterized in HuH7 cells and hydrodynamically injected mice. Results: Of 61 OBI sequences, 34 (55.7%) harbored MHR mutations, which was significantly higher than the frequency in either the HBsAg-L (34.0%, p = 0.003) or the HBsAg-H group (17.1%, p <0.001). Alterations in antigenicity induced by the 13 representative MHR mutations identified in the OBI group were assessed by reacting recombinant HBV mutants with 30 different MAbs targeting various epitopes. Four out of the 13 mutations (C124R, C124Y, K141E, and D144A) strongly decreased the analytical sensitivity of seven commercial HBsAg immunoassays, and 10 (G119R, C124Y, I126S, Q129R, S136P, C139R, T140I, K141E, D144A, and G145R) significantly impaired virion and/or S protein secretion in both HuH7 cells and mice. Conclusions: MHR mutations alter antigenicity and impair virion secretion, both of which may contribute to HBsAg detection failure in individuals with OBI. ? 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84984550248&doi=10.1016%2fj.jhep.2012.05.009&partnerID=40&md5=95e8cc7cd43042edd458391680db06bf https://scholars.lib.ntu.edu.tw/handle/123456789/568507 |
ISSN: | 0168-8278 | DOI: | 10.1016/j.jhep.2012.05.009 | SDG/關鍵字: | alanine; arginine; aspartic acid; cysteine; epitope; glutamic acid; glutamine; glycine; hepatitis B surface antigen; isoleucine; lysine; monoclonal antibody; proline; serine; threonine; tyrosine; vitronectin; adult; amino acid substitution; animal experiment; antigenicity; article; blood donor; blood sampling; cell line; clinical assessment; controlled study; enzyme linked immunosorbent assay; female; gene frequency; gene mutation; gene sequence; hepatitis B; Hepatitis B virus; human; human cell; hydrodynamics; hydrophilicity; immunoassay; in vitro study; in vivo study; major clinical study; major hydrophilic region; male; mouse; nonhuman; occult blood; occult hepatitis B virus infection; phenotype; priority journal; protein blood level; protein secretion; sensitivity and specificity; virion; virus load; virus recombinant; virus strain |
顯示於: | 臨床醫學研究所 |
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