Chen Bing-Fang
Bing-Fang Chen, School of Medicine, Fu Jen Catholic University, New Taipei City 24205, Taiwan.
World J Gastroenterol. 2016 Sep 21;22(35):8041-9. doi: 10.3748/wjg.v22.i35.8041.
To investigate the associations of different types of pre-S deletions with hepatitis B virus (HBV) genotypes.
The sequences of the pre-S region, basal core promoter (BCP) mutation, and precore (PC) mutation were examined through direct DNA sequencing or clonal analysis and sequencing in 273 HBV carriers, namely 55 asymptomatic carriers, 55 carriers with chronic hepatitis (CH), 55 with liver cirrhosis (LC), 53 with liver cirrhotic hepatocellular carcinoma (LC-HCC), and 55 with noncirrhotic HCC. A total of 126 HBV carriers (46.2%) harbored pre-S deletions. The DNA sequences of pre-S deletion mutants from 43 age-matched genotype B (HBV/B)-infected carriers and 43 age-matched genotype C (HBV/C)-infected carriers were further examined, aligned, and compared.
No significant difference was observed in the mean age distribution (P = 0.464), male sex (P = 0.805), viral load (P = 0.635), or BCP mutation (P = 0.117) between the HBV/B and HBV/C groups. However, the rate of PC mutation was significantly higher in the HBV/B-infected carriers than in the HBV/C-infected carriers (P = 0.003). Both genotypes exhibited a high rate of deletion in the C-terminal half of the pre-S1 region and N-terminus of the pre-S2 region (86.0% and 79.1% in the HBV/B group; 69.8% and 72.1% in the HBV/C group, respectively). Epitope mapping showed that deletion in several epitope sites was frequent in both genotypes, particularly pS1-BT and pS2-B2. Conversely, the rate of pS2-B1 deletion was significantly higher in the HBV/B group (72.1% vs 37.2%, P = 0.002), and the rate of pS2-T deletion was significantly higher in the HBV/C group (48.8% vs 25.6%, P = 0.044). Functional mapping showed that the rate of deletion in three functional sites (the nucleocapsid binding site, start codon of M, and site for viral secretion) located in the N-terminus of the pre-S2 region was significantly higher in the HBV/B group (P < 0.05). One type of N-terminus pre-S1 deletion mutant with deletion of the start codon of the L protein was frequently observed in the HBV/C group (20.9% vs 9.3%, P = 0.228), particularly in the LC patients (42.9% vs 12.5%). Different patterns of pre-S deletions were also found between the HBV/B and HBV/C groups according to different clinical outcomes. In CH patients, deletion in the site for polymerized human serum albumin was more frequent in the HBV/B group (88.9% vs 36.4%, P = 0.028). In the LC-HCC patients, the rate of deletion in the pre-S2 region was significantly higher in the HBV/B group than in the HBV/C group (P < 0.05).
HBV/B- and HBV/C-infected carriers exhibit different patterns of pre-S deletion, which may be associated with the progression of liver diseases.
研究不同类型的前S区缺失与乙型肝炎病毒（HBV）基因型之间的关联。
通过直接DNA测序或克隆分析及测序，检测了273例HBV携带者的前S区序列、核心启动子（BCP）突变和前核心（PC）突变，这些携带者包括55例无症状携带者、55例慢性肝炎（CH）携带者、55例肝硬化（LC）患者、53例肝硬化肝细胞癌（LC-HCC）患者和55例非肝硬化肝癌患者。共有126例HBV携带者（46.2%）存在前S区缺失。进一步检测、比对并比较了43例年龄匹配的B基因型（HBV/B）感染携带者和43例年龄匹配的C基因型（HBV/C）感染携带者的前S区缺失突变体的DNA序列。
HBV/B组和HBV/C组在平均年龄分布（P = 0.464）、男性比例（P = 0.805）、病毒载量（P = 0.635）或BCP突变（P = 0.117）方面未观察到显著差异。然而，HBV/B感染携带者的PC突变率显著高于HBV/C感染携带者（P = 0.003）。两种基因型在前S1区C端一半和前S2区N端的缺失率均较高（HBV/B组分别为86.0%和79.1%；HBV/C组分别为69.8%和72.1%）。表位图谱显示，两种基因型中几个表位位点的缺失较为常见，尤其是pS1-BT和pS2-B2。相反，HBV/B组中pS2-B1缺失率显著更高（72.1%对37.2%，P = 0.002），HBV/C组中pS2-T缺失率显著更高（48.8%对25.6%，P = 0.044）。功能图谱显示，位于前S2区N端的三个功能位点（核衣壳结合位点、M蛋白起始密码子和病毒分泌位点）的缺失率在HBV/B组显著更高（P < 0.05）。一种L蛋白起始密码子缺失的N端前S1区缺失突变体在HBV/C组中经常出现（20.9%对9.3%，P = 0.228），尤其在LC患者中（42.9%对12.5%）。根据不同的临床结局，HBV/B组和HBV/C组之间也发现了不同的前S区缺失模式。在CH患者中，HBV/B组中聚合人血清白蛋白位点的缺失更为频繁（88.9%对36.4%，P = 0.028）。在LC-HCC患者中，HBV/B组前S2区的缺失率显著高于HBV/C组（P < 0.05）。
HBV/B和HBV/C感染携带者表现出不同的前S区缺失模式，这可能与肝脏疾病的进展有关。
