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Influence of mutations in hepatitis B virus surface protein on viral antigenicity and phenotype in occult HBV strains from blood donors
Huang, Cheng-Hao ; Yuan, Quan ; Chen, Pei-Jer ; Zhang, Ya-Li ; Chen, Chang-Rong ; Zheng, Qing-Bing ; Yeh, Shiou-Hwei ; Yu, Hai ; Xue, Yu ; Chen, Yi-Xin ; Liu, Ping-Guo ; Ge, Sheng-Xiang ; Zhang, Jun ; Xia, Ning-Shao
2012-10
关键词HBsAg mutants Occult HBV infection Antigenicity Secretion deficiency
英文摘要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, T1401, 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. (C) 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.; Excellent Youth Foundation of the Fujian Scientific Committee [2009J06020]; National Science Fund for Distinguished Young Scholars [30925030]; National Scientific and Technological Major Project [2012ZX10002-005/2012ZX10004-503]
语种英语
出版者ELSEVIER SCIENCE BV
内容类型期刊论文
源URL[http://dx.doi.org/10.1016/j.jhep.2012.05.009]  
专题生命科学-已发表论文
推荐引用方式
GB/T 7714
Huang, Cheng-Hao,Yuan, Quan,Chen, Pei-Jer,et al. Influence of mutations in hepatitis B virus surface protein on viral antigenicity and phenotype in occult HBV strains from blood donors[J],2012.
APA Huang, Cheng-Hao.,Yuan, Quan.,Chen, Pei-Jer.,Zhang, Ya-Li.,Chen, Chang-Rong.,...&Xia, Ning-Shao.(2012).Influence of mutations in hepatitis B virus surface protein on viral antigenicity and phenotype in occult HBV strains from blood donors..
MLA Huang, Cheng-Hao,et al."Influence of mutations in hepatitis B virus surface protein on viral antigenicity and phenotype in occult HBV strains from blood donors".(2012).
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