丙型肝炎病毒(HCV)膜区基因在系列血清中的变异研究

Study on Gene Variation of HCV Envelope Region in Serial Sera

目的 研究HCV基因随时间推移产生的变化。方法 利用不同HCVE2区引物对 4例病人系列血清标本进行序列测定和比较 ,并用不同方法确定HCV基因型别。结果 用不同引物扩增、测序表明 4例病人基因均为 1b和 2a型基因 ,随时间推移发生型别转换 ,推测与混合感染有关 ,在 2型转换期有 1b/ 2a混合感染现象。同一病人同型HCV膜区基因随时间推移有核苷酸和氨基酸改变 ,但变异程度相对较小 ,但有一定规律性 ,表现为在膜区高变区有些氨基酸位点较保守 ,所测的两型HCV保守位点相同 ,在同一位点的氨基酸变化趋于相同。结论 本研究结果提示HCV基因变化是多层次的 ,首先是不同基因型变化 ,其次是基因本身序列变化 ,且变化具有一定规律性。

Objective To study the HCV gene variation with time.Methods The envelope gene of the serial sera from 4 HCV infected patients were amplified and sequenced with different primers (HVR1b, HVR2a, HSP1b, HSP2a).Genotypes of the sera were tested by RT-PCR based method and the sequencing of 5′-UTR, Core and E region.Results All the serial sera of 4 patients were infected by 1b and 2a genes, and genotype changing with time, the mixed infection was found in the samples during the exchanged period. The same types and sequences were found when amplified and sequenced with HVR1b, HVR2a primers,respectively, whereas different types were obtained from the 1b/2a mixed samples using HSP1b and HSP2a. The nucleotide and amino acid sequences of the same genotype from the same serum of a patient changed with time.Conclusion The results indicated that HCV gene sequences varied at different levels,genotype changes at a higher level and gene sequence change at a lower level.