“a”决定因素突变对中国乙型肝炎病毒乙型肝炎病毒乙型肝

StephenW

J Med Virol. 2017 May 17. doi: 10.1002/jmv.24859. [Epub ahead of print]
Impact of "a" Determinant Mutations on Detection of Hepatitis B Surface Antigen (HBsAg) in HBV Strains from Chinese Patients with Occult Hepatitis B.
Huang X1, Ma C2, Zhang Q3, Shi Q4, Huang T5, Liu C1, Li J1, Hollinger FB6.
Author information

1    Department of Blood Transfusion, The General Hospital of Jinan Military Command, Jinan, China.
2    Department of Medical Laboratory, Shanghai Seventh People's Hospital, Shanghai, China.
3    Department of Orthopedics, The General Hospital of Jinan Military Command, Jinan, China.
4    Department of Laboratory Diagnostics, Jinan Infectious Disease Hospital, Jinan, China.
5    Department of Viral Diseases, Shandong Center for Disease Control and Prevention, Jinan, China.
6    Departments of Molecular Virology & Microbiology and Medicine, Baylor College of Medicine, Houston, Texas, USA.

Abstract

This study was designed to detect mutations that occur within the "a" determinant in the S gene of the hepatitis B virus (HBV) in patients with occult hepatitis B (OHB), and to analyze the influence of these mutations on expression and reactivity of the hepatitis B surface antigen (HBsAg). Twenty-three certified OHB samples were compared to 32 HBsAg positive samples from patients with chronic hepatitis B. The median HBV DNA levels in the OHB group were significantly lower than those in the control group (p < 0.0001). Mutations within the "a" determinant were analyzed by gene amplification and sequencing. This revealed mixed infections in which clones within a sample displayed either different mutations or mutations in association with clones that exhibited wild type amino acid patterns. Sequencing analysis also showed a significant difference between the proportions of amino acid mutations observed in the OHB and control groups. Seven recombinant S (rS) proteins with corresponding OHB mutations and three wild type alleles were expressed and purified in the Pichia pastoris expression system to preserve conformational attributes, and their reactivity analyzed using six commercial HBsAg assays. The OHB sera were HBsAg nonreactive while the rS proteins with corresponding OHB mutations were universally reactive. Thus, we postulate that the reduced binding affinity between mutated HBsAg and its antibody may not be as important in defining OHB as is the effect of specific mutations in the preS/S region of the genome that affect the synthesis and secretion of the S protein and/or the virion. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.
KEYWORDS:

Enzyme assays; Hepatitis B virus; Inapparent infection; Mutation

PMID:
    28513915
DOI:
    10.1002/jmv.24859

StephenW

J Med Virol 2017年5月17日。doi：10.1002 / jmv.24859。 [提前印刷]
“a”决定因素突变对中国乙型肝炎病毒乙型肝炎病毒乙型肝炎表面抗原（HBsAg）检测的影响
黄X1，马C2，张三，史Q4，黄T5，刘C1，李杰1，霍林格FB6。
作者信息

1济南军区总医院血液输血管理部，济南。
2中国上海市第七人民医院医学实验室。
3济南军区总医院骨科，济南。
4济南传染病医院实验室诊断系，济南。
山东省疾病预防控制中心病毒学系，济南，济南。
美国得克萨斯州休斯敦贝勒医学院分子病毒学和微生物学与药物学系6个部门。

抽象

本研究旨在检测隐匿性乙型肝炎（OHB）患者乙型肝炎病毒（HBV）的S基因“a”决定因素中发生的突变，并分析这些突变对表达和反应性的影响乙型肝炎表面抗原（HBsAg）。将23例认证的OHB样品与来自慢性乙型肝炎患者的32例HBsAg阳性样品进行比较.HBB组的HBV DNA中位数显着低于对照组（p <0.0001）。通过基因扩增和测序分析“a”决定簇内的突变。这揭示了混合感染，其中样品中的克隆显示与展示野生型氨基酸模式的克隆相关联的不同突变或突变。测序分析也显示OHB和对照组之间观察到氨基酸突变的比例有显着差异。在巴斯德毕赤酵母表达系统中表达和纯化具有相应OHB突变的7种重组S（rS）蛋白和3种野生型等位基因，以保持构象属性，并使用六种商业HBsAg测定分析其反应性。 OHB血清是HBsAg非反应性的，而具有相应OHB突变的rS蛋白是普遍反应性的。因此，我们假设突变的HBsAg与其抗体之间降低的结合亲和力在定义OHB中可能不一样重要，因为影响S蛋白的合成和分泌的基因组的前S / S区域中的特异性突变的影响，以及/或病毒粒子。本文受版权保护。版权所有。

本文受版权保护。版权所有。
关键词：

酶测定;乙型肝炎病毒不明显感染突变

结论：
    28513915
DOI：
    10.1002 / jmv.24859