丙型肝炎病毒高变区序列变化及其临床意义

Sequence Variations of the Hypervariable Region of HCV and Their Clinical Significance

目的 了解HCV慢性感染过程中高变区序列变化及其临床意义。方法 对 8例急性丙肝及 2 0例慢性丙肝随访 2年 ,相隔半年抽血 ,用逆转录多聚酶联反应及直接序列法分析不同时期HCV HVR的序列变化。结果 2 8例丙肝的HVR序列均有不同程度的变化 ,92 %变化的核苷酸导致相应氨基酸的变化 ,仅 8%为同义替换 ,2 7个氨基酸的每年变化范围为 1～ 2 0 ,平均 8个 (30 % ) ,HVR密码子中 ,以第一及第二变化最为常见 ,分别为 6 2 %及 31%。急性肝炎年基因位点为 0 .89× 10 -1,慢性丙肝年基因位点为 2 .31× 10 -1,两者有统计意义。年基因位点与HCV亚型无关。ALT反复波动者的HVR变异率明显高于ALT相对稳定者。结论 在HCV感染过程中 ,HVR序列变化可能是HCV为逃避人体免疫系统作用的一种适应性反应 ,在HCV持续感染及肝炎发作中 。

Purpose To understand the clinical significance of sequence variations in the hypervariable region(HVR) of hepatitis C virus during infections. Methods 8 cases of acute hepatitis C and 20 of chronic hepatitis C were followed for two years.Blood samples were taken at intervals of six months for analysis of HCV?HVR sequences by reverse transcription polymerase chain reaction(RT?PCR) and direct sequencing methods. Results Results showed that HCV?HVR sequences of the 28 patients changed in various degrees.92% of these nucleotide substitutions led to changes of corresponding amino acid sequences.Only 8% of changed nucleotide were synonymous substitutions.Variation of amino acid ranged from 1 to 20(mean 8,30%).The most common nucleotide substitution(62%) occurred in the first position of codon,31% in the second and the rest in the third.HVR variation rate was 0.89×10 -1 per genome site per year in acute hepatitis C,compared with 2.31×10 -1 per genome site per year in chronic hepatitis C ( P <0.05),but variations had no relation to HCV subtype.Variation of HVR in the flare up type (ALT>150 u/L) was much more than that in the quiescent type (ALT<100 u/L). Conclusions Our results suggested that sequence variation of HVR during HCV chronic infection seems to be an adaptive response to HCV to evade the host immune pressure and might play a major role in the establishment of persistent infection as well as in the flare up of hepatitis.