Effects of amino acid substitutions in hepatitis B virus surface protein on virion secretion, antigenicity, HBsAg and viral DNA.
Effects of amino acid substitutions in hepatitis B virus surface protein on virion secretion, antigenicity, HBsAg and viral DNA.
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DOI：
10.1016/j.jhep.2016.09.005
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发表时间：
2017-03
影响因子：
25.7
通讯作者：
Li T
中科院分区：
文献类型：
--
作者：
Xiang KH;Michailidis E;Ding H;Peng YQ;Su MZ;Li Y;Liu XE;Dao Thi VL;Wu XF;Schneider WM;Rice CM;Zhuang H;Li T
慢性B型肝炎（CH B）患者血清HBsAg和HBV DNA水平波动较大，是重要的病毒学标志物。本研究的目的是揭示小分子B型肝炎表面蛋白（SHBs）氨基酸（AA）置换对血清HBsAg和HBV DNA水平的潜在影响及其机制。对230例未经治疗的C基因型慢性B型肝炎患者的血清标本进行了HBV DNA水平、HBV感染血清学标志物和SHBs序列分析。对鉴定的SHB突变体进行体外功能分析。在230个SHBs序列中，有39个（16.96%）序列未检测到突变（野生型，WT），191个（83.04%）序列存在单一或多个突变。SHB由226个AA组成，其中104个（46.02%）在我们的研究中有突变。某些突变（如sE 2G、sL 21 R、sG 24 K、sT 47 A/K、sC 69 stop（sC 69 *）、sL 95 W、sL 98 V和sG 145 R）与血清HBsAg水平呈负相关。HBsAg与HBVDNA水平呈正相关（r = 0.61，P < 0.001）。体外分析表明，这些突变通过限制病毒体分泌和抗体结合能力降低细胞外HBsAg和HBV DNA水平。通过共表达WT HBsAg可以拯救sE 2G、sC 69 * 和sG 145 R的病毒体分泌。在未经治疗的CHB患者中，在主要抗原区域外有新的SHB突变的患者血清HBsAg水平低于没有突变的患者。潜在机制包括病毒体分泌受损和与用于HBsAg测量的抗体的结合亲和力降低。
As important virological markers, serum HBsAg and HBV DNA levels show large fluctuations among chronic hepatitis B (CHB) patients. The aim of this study was to reveal the potential impact and mechanisms of amino acid (AA) substitutions in small hepatitis B surface proteins (SHBs) on serum HBsAg and HBV DNA levels. Serum samples from 230 untreated chronic hepatitis B patients with genotype C HBV were analyzed in terms of HBV DNA levels, serological markers of HBV infection and SHBs sequences. In vitro functional analysis of the identified SHBs mutants was performed. Among 230 SHBs sequences, there were 39 (16.96%) sequences with no mutation detected (wild-type, WT) and 191 (83.04%) with single or multiple mutations. SHBs consist of 226 AAs, of which 104 (46.02%) had mutations in our study. Some mutations (e.g. sE2G, sL21R, sG24K, sT47A/K, sC69stop (sC69*), sL95W, sL98V, and sG145R) negatively correlated with serum HBsAg levels. HBsAg and HBV DNA levels from this group of patients had a positive correlation (r = 0.61, p < 0.001). In vitro analysis showed that these mutations reduced extracellular HBsAg and HBV DNA levels by restricting virion secretion and antibody binding capacity. Virion secretion could be rescued for sE2G, sC69*, and sG145R by co-expression of WT HBsAg. The serum HBsAg levels were lower in untreated CHB patients with novel SHBs mutations outside the major antigenic region than those without mutations. Underlying mechanisms include impairment of virion secretion and lower binding affinity to antibodies used for HBsAg measurements.
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影响因子：
25.7
作者：
Nguyen, Tin;Thompson, Alexander J. V.;Locarnini, Stephen A.
通讯作者：
Locarnini, Stephen A.
影响因子：
25.7
作者：
Huang, Cheng-Hao;Yuan, Quan;Xia, Ning-Shao
通讯作者：
Xia, Ning-Shao
影响因子：
8.8
作者：
Verheyen, Jens;Neumann-Fraune, Maria;Obermeier, Martin
通讯作者：
Obermeier, Martin
影响因子：
3.1
作者：
Deguchi, M;Yamashita, N;Mushahwar, IK
通讯作者：
Mushahwar, IK
影响因子：
3.2
作者：
Hao, Ran;Xiang, Kuanhui;Li, Tong
通讯作者：
Li, Tong