Influence of mutations in hepatitis B virus surface protein on viral antigenicity and phenotype in occult HBV strains from blood donors
Influence of mutations in hepatitis B virus surface protein on viral antigenicity and phenotype in occult HBV strains from blood donors
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DOI：
10.1016/j.jhep.2012.05.009
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发表时间：
2012-10-01
影响因子：
25.7
通讯作者：
Xia, Ning-Shao
中科院分区：
文献类型：
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作者：
Huang, Cheng-Hao;Yuan, Quan;Xia, Ning-Shao
背景和目标：为探讨隐匿性B肝炎病毒（HBV）感染（OBI）时HBsAg的变异及其对病毒抗原性和表型的影响，对38，499名献血员中61例OBI携带者（OBI组）和153例HBsAg（+）且血清HBsAg <100 IU/ml（HBsAg Ag-H组）的特征进行了研究。确定病毒序列的主要亲水区（MHR）中的突变。在OBI序列中观察到的13个代表性MHR突变用一组单克隆抗体（MAb）和商业HBsAg免疫测定进行抗原性表征，并在HuH 7细胞和水动力注射小鼠中进行功能性表征。在61个OBI序列中，（55.7%）携带MHR突变，这显著高于MHR基因突变的频率，（34.0%，p = 0.003）或Ag-H组（17.1%，p < 0.001）。通过将重组HBV突变体与靶向不同表位的30种不同MAb反应，评估了OBI组中鉴定的13种代表性MHR突变诱导的抗原性变化。13种突变中有4种（C124 R，C124 Y，K141 E和D144 A）强烈降低了7种商业HBsAg免疫测定的分析灵敏度，（G119 R、C124 Y、I126 S、Q129 R、S136 P、C139 R、T1401、K141 E、D144 A、结论：MHR突变改变了抗原性并损害了病毒颗粒的分泌，这两者都可能导致OBI患者HBsAg检测失败。(C)2012年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
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-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.