丙型肝炎病毒高变区序列变化及其临床意义

摘要

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.%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20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 28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，27个氨基酸的每年变化范围为1～20，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62%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，可能也起着主要的作用。