Roque-Afonso Anne Marie, Férey Marie-Pierre, Ly Thoai Duong, Graube Arielle, Costa-Faria Luciana, Samuel Didier, Dussaix Elisabeth
INSERM U785, 94804 Villejuif, France.
Antivir Ther. 2007;12(8):1255-63.
Understanding the prevalence of potential antigenic variation of the hepatitis B virus (HBV) surface antigen (HBsAg) is fundamental for assay design and to future changes in vaccine formulation. In this study, the nature and frequency of HBsAg polymorphisms occurring in France in chronic carriers and in newly diagnosed patients were determined. We focused on variations in the major hydrophilic region (MHR), the central core of HBsAg known to be exposed on the surface and involved in antibody binding.
Two patient groups were identified: 51 chronic HBV carriers followed at our institution for > 1 year; and 129 newly diagnosed patients (63 of whom had a first HBsAg-positive result at our hospital laboratory and 66 a first positive result in a private laboratory). DNA sequences of HBsAg were obtained from these 180 patients and compared with consensus sequences built with 168 full-length HBV sequences imported from GenBank. Polymorphisms of the MHR of HBsAg were analysed with the Mutation Master Software. Literature review and BLOSUM scores were used to define potentially altered antigenicity.
The global frequency of MHR variants was 27.8%. Occurrence of MHR variants was independent of viral load, HBeAg status and sex, but was associated with the chronic carriers' group, advancing age, the presence of antibodies to HBsAg, immunoprophylaxis administration, antiviral treatment and genotypic resistance to antivirals. In multivariate analysis, the independent variables associated with MHR variants were advancing age and the presence of genotypic resistance to nucleoside or nucleotide analogues.
Most MHR variants emerge with longer disease duration and upon indirect selective pressure. Variation of the MHR may serve to restore virus replication of resistant strains. Combined envelope and polymerase variants could impair diagnostic assays and limit treatment alternatives.
了解乙型肝炎病毒（HBV）表面抗原（HBsAg）潜在抗原变异的流行情况，对于检测方法的设计以及未来疫苗配方的改变至关重要。在本研究中，我们确定了法国慢性携带者和新诊断患者中HBsAg多态性的性质和频率。我们重点关注主要亲水区（MHR）的变异，MHR是HBsAg的核心区域，已知其暴露于表面并参与抗体结合。
确定了两个患者组：51名在我们机构随访超过1年的慢性HBV携带者；以及129名新诊断患者（其中63名在我们医院实验室首次检测到HBsAg阳性结果，66名在私立实验室首次检测到阳性结果）。从这180名患者中获取HBsAg的DNA序列，并与从GenBank导入的168条全长HBV序列构建的共有序列进行比较。使用Mutation Master软件分析HBsAg的MHR多态性。通过文献综述和BLOSUM评分来定义潜在的抗原性改变。
MHR变异的总体频率为27.8%。MHR变异的发生与病毒载量、HBeAg状态和性别无关，但与慢性携带者组、年龄增长、抗HBsAg抗体的存在、免疫预防接种、抗病毒治疗以及抗病毒药物的基因型耐药性有关。在多变量分析中，与MHR变异相关的独立变量是年龄增长以及对核苷或核苷酸类似物的基因型耐药性。
大多数MHR变异随着疾病持续时间延长和间接选择压力而出现。MHR的变异可能有助于恢复耐药菌株的病毒复制。包膜和聚合酶变异的联合作用可能会损害诊断检测并限制治疗选择。
