丙型肝炎病毒感染自然过程中的准种变化

Positive selection caused change of hepatitis C virus quasispecies distribution in the natural history of he patitis C infection

目的观察丙型肝炎病毒(HCV)持续感染者与自然阴转者外周血HCV准种构成的变化规律。方法应用基因扩增、分子克隆和测序的方法,对未接受过治疗的4例HCV持续感染者与4例自然阴转者前后间隔10年血清中HCV高变区1(HVR1)基因片段进行了序列分析及遗传进化关系比较。结果与持续感染者相比,自然阴转者外周血HCVHVR1区准种群体组内平均遗传距离、熵值较小。4例持续感染者中有3例10年前后血清HCVHVR1准种群体组内与组间遗传距离有明显差异。8例感染者中有7例血清HCV准种KA/KS值大于1。结论在丙型肝炎的自然病程中HCV准种遗传复杂度、变异度大小可能与丙型肝炎的转归相关;HCV准种构成可能发生改变。

Objective To investigate the evolution of hepatitis C virus (HCV) quasispecies in persistent and self limited infection patients. Methods Peripheral blood HCV preserved for 10 years from 8 naive individuals once infected by HCV were analyzed. HCV hypervariable region 1 (HVR1) genes were cloned and sequenced. Entropy, genetic distances, nonsynonymous mutations per nonsynonymous site (K A ), synonymous mutations per synonymous site(K S ) were evaluated for evolutionary analysis. Results The entropy values and genetic distances of HCV quasispecies were lower in self limited infection indivi duals than that of persistent infection individuals. In 3 of the 4 persistent infection individuals there exist no difference between within group and between group genetic distances in HCV HVR1. The ratios of K A /K s were higher than 1 in 7 of these 8 individuals. Conclusions The complexity and diversity degree of HCV quasispecies may affect the outcome of HCV infection. Positive Darwinian selection may be the major cause for the change of HCV quasispecies distribution in hepatitis C infection natural history.