丙型肝炎病毒NS5A基因变异与干扰素疗效的关系

Mutations in nonstructural 5A gene of hepatitis C virus and its response to interferon alfa

目的:探讨HCV1b型慢性丙型肝炎患者HCV NS5A基因变异与干扰素(IFN)疗效的关系,NS5A_(2209-2248)片断是否存在干扰素敏感决定区(ISDR)。方法:留取慢性丙型肝炎患者干扰素治疗前血清,应用RT-PCR法扩增NS5A基因片段,用直接测序法进行核苷酸及氨基酸序列测定。结果:11例HCV1b型患者中1例为中间型,其余为野生型。2例表现为完全应答,均为野生型,9例为无应答。两组之间核苷酸及氨基酸序列无显著差异。对1例患者的动态观察发现,干扰素治疗后其核苷酸及氨基酸序列均有所变化,改变了其在基因树中的位置。结论:HCV1b型NS5A基因变异与干扰素疗效无关,NS5A_(2209-2248)区高度保守。未证实存在ISDR。干扰素治疗可引起HCV准种改变。

AIM: To investigate the relationship between NS5A_(2209-2248) sequences and response to interferon therapy,and whether there is an IFN sensitivity determining region(ISDR)in the region of NS5A_(2209-2248). METHODS: We analyzed 11 patients with chronic HCV 1b infection who had received interferon alfa therapy for six months.Pretreatment serum samples were analyzed.The amino acid sequence of NS5A_(229-2248)was determined by direct sequencing of the HCV genome amplified by the polymerase chain reaction. RESULTS: Among the 11 patients,only 1 was intermediate type,all the others were wild type.2 of wild type patients showed complete response.Others were nonresponders. There was no significant difference in nucleotide and amino acid sequences between the two groups.The nucleotide and amino acid sequences changed after IFN treatment in one nonresponder. CONCLUSION: The NS5A_(2209-2248)region was highly conservative.In Chinese patients with chronic HCV 1b infection,there was no correlation between response to in- terferon and mutations in the NS5A gene.HCV quasispecies changed after IFN therapy.