Department of Medical Virology, University of Pretoria/Tshwane Academic Division of NHLS, Pretoria, South Africa.
J Med Virol. 2013 Nov;85(11):1883-92. doi: 10.1002/jmv.23695. Epub 2013 Aug 7.
Hepatitis B virus (HBV) is a serious global health problem, and HBV genotype is an important determinant of disease progression and treatment outcome. The aim of this study was to assess variations of the precore/core (preC/C) region in HBV genotype A. Sequencing of the preC/C and surface (S) genes of HBV was performed on plasma samples from 20 HBV/HIV co-infected and 5 HBV mono-infected individuals. All preC/C study sequences clustered with subgenotype A1, except for two which clustered with subgenotype D4 reference strains. The nucleotide and amino acid variability was far higher in the preC/C region than in the S region. Mutations associated with reduction or failure of HBV e-antigen (HBeAg) production were observed, with a preC start codon mutation being common (24%). Other mutations (e.g., P5H/L and I97L) associated with severe liver disease were also noticed, some of which were located in the major histocompatibility restricted sites. PreC/C intergenotype nucleotide divergence was >7%, while subgenotypes differed by 2.5-7%. Several study sequences were highly divergent from other African subgenotype A1 strains. This study showed that HBeAg-negative chronic hepatitis B is underestimated in subgenotype A1, and also highlighted the variant South African A1 strains. The major advantage of preC/C sequencing is that it informs patient management as HBeAg-negative chronic hepatitis B responds poorly to conventional interferon-α therapy, and some guidelines treat HBeAg-negative chronic hepatitis B differently from HBeAg-positive chronic hepatitis B. These data suggest that subgenotype A1 may be more involved in severe HBV-related diseases.
乙型肝炎病毒（HBV）是一个严重的全球健康问题，HBV 基因型是疾病进展和治疗结果的重要决定因素。本研究旨在评估乙型肝炎病毒基因型 A 中前核心/核心（preC/C）区的变异情况。对 20 例乙型肝炎病毒/艾滋病病毒合并感染和 5 例乙型肝炎病毒单感染个体的血浆样本进行了 HBV preC/C 和表面（S）基因的测序。除了 2 个与亚基因型 D4 参考株聚类的序列外，所有 preC/C 研究序列均聚类为亚基因型 A1。preC/C 区的核苷酸和氨基酸变异性远远高于 S 区。观察到与 HBV e 抗原（HBeAg）产生减少或失败相关的突变，preC 起始密码子突变很常见（24%）。还注意到与严重肝病相关的其他突变（如 P5H/L 和 I97L），其中一些位于主要组织相容性受限部位。preC/C 种间核苷酸差异>7%，而亚基因型差异为 2.5-7%。一些研究序列与其他非洲亚基因型 A1 株高度不同。本研究表明，亚基因型 A1 中 HBeAg 阴性慢性乙型肝炎被低估，同时也强调了南非 A1 变异株。preC/C 测序的主要优点是它可以告知患者管理，因为 HBeAg 阴性慢性乙型肝炎对常规干扰素-α治疗反应不佳，一些指南对 HBeAg 阴性慢性乙型肝炎的治疗与 HBeAg 阳性慢性乙型肝炎不同。这些数据表明，亚基因型 A1 可能更多地参与严重的乙型肝炎病毒相关疾病。
