Zhang KaiYu, Imazeki Fumio, Fukai Kenichi, Arai Makoto, Kanda Tatsuo, Mikata Rintaro, Yokosuka Osamu
Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan.
J Med Virol. 2007 Jun;79(6):683-93. doi: 10.1002/jmv.20849.
To investigate the relationship between viral factors and the development of chronic hepatitis B, the entire hepatitis B virus (HBV) genome of chronic carriers at different disease stages were analyzed. Eighty genotype C HBV carriers including 12 hepatitis B e antigen (HBeAg) positive asymptomatic carriers (Group A), 49 HBeAg positive patients with chronic liver diseases (Group B) and 19 anti-HBe positive patients with chronic liver diseases (Group C) were studied. HBV nucleic acid from serum samples was sequenced directly and compared with GenBank reference sequences HBV X01587 and M12906. On phylogenetic analysis, 76 cases were genotype C2. Of the 76 genotype C2 cases, the nucleotide and amino acid substitution rates in the precore/core region were significantly higher in Groups B and C than in Group A, also in Group C than in Group B. The nucleotide substitution rates in the full genome and the core promoter region were significantly higher in Group C than in Group A, also in group C than in Group B. The nucleotide and amino acid substitution rates in the X region were significantly higher in Group C than in Group A. The amino acid substitution rate in the pre-S2 region was significantly higher in Group C than in Group B. Deletion mutations were found mainly in Groups B and C. This whole genome analysis of HBV chronic carriers suggested that the nucleotide substitutions and deletions in HBV were closely associated with the pathogenesis of chronic HBV infection.
为了研究病毒因素与慢性乙型肝炎发展之间的关系，对处于不同疾病阶段的慢性携带者的整个乙型肝炎病毒（HBV）基因组进行了分析。研究了80例C基因型HBV携带者，其中包括12例乙型肝炎e抗原（HBeAg）阳性无症状携带者（A组）、49例HBeAg阳性慢性肝病患者（B组）和19例抗-HBe阳性慢性肝病患者（C组）。对血清样本中的HBV核酸进行直接测序，并与GenBank参考序列HBV X01587和M12906进行比较。系统发育分析显示，76例为C2基因型。在这76例C2基因型病例中，B组和C组在前核心/核心区域的核苷酸和氨基酸替代率显著高于A组，C组也高于B组。C组在全基因组和核心启动子区域的核苷酸替代率显著高于A组，也高于B组。C组在X区域的核苷酸和氨基酸替代率显著高于A组。C组在前S2区域的氨基酸替代率显著高于B组。缺失突变主要出现在B组和C组。对HBV慢性携带者的全基因组分析表明，HBV中的核苷酸替代和缺失与慢性HBV感染的发病机制密切相关。
