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目的 初步探讨HBV基因S区的准种特点与乙型肝炎病毒(HBV)感染临床转归的关系.方法 选择慢性HBV携带者、慢性乙型肝炎患者、慢性重型肝炎患者各3例,所有患者均为男性,且HBV基因型均为C型.扩增患者血清中HBV基因S区片段并克隆,每份样本挑选20个克隆进行测序,并用SPSS 15.0软件进行统计分析.结果 慢性HBV携带者以及慢性乙型肝炎患者的HBV基因S区准种复杂度小于慢性重型乙型肝炎患者,但差异无统计学意义(t=1.7,P=0.26).对于HBV S区T细胞表位的第45、47和85位氨基酸,慢性乙型肝炎患者的准种构成情况比HBV携带者复杂(P=0.01),与慢性重型乙型肝炎的差别无统计学意义(P=0.06),计算机模拟分析提示优势克隆和非优势克隆的T细胞表位均能与CTL受体有效结合.结论 HBV基因S区部分T细胞表位的准种构成差异可能与HBV慢性感染的临床转归相关.

Objective To investigate the association of hepatitis B virus(HBV) S gene quasispecies with the outcome of HBV infection.Methods Serum samples were collected from three chronic HBV carriers, three chronic hepatitis B and three chronic severe hepatitis B patients.All subjects were male and with HBV genotype C.HBV S gene was amplified, and 20 clones of HBV fragment were randomly selected and sequenced from each sample.SPSS 15.0 software was adopted for analysis.Results Quasispecies complexity of HBV S gene in chronic HBV carriers and chronic hepatitis B tended lower than that of the severe chronic hepatitis B, but the difference was not of statistical significance (P＞0.05).In T cell epitope 45, 47, 85 amino acid sites of the HBV S gene, the constitution of quasispecies in the chronic hepatitis B was more complex than that of the HBV carriers (P=0.01), but compared with the severe chronic hepatitis, the difference was not significant (P=0.06).The computer model showed that both the dominant clones and the non dominant clones could effectively bind to the receptors of cytotoxic T lymphocytes.Conclusion Quasispecies in some T cell epitopes of HBV S gene may be related with the clinical outcome of hepatitis B.