兰州地区丙型肝炎病毒基因变异与干扰素α应答关系的探讨

Study on the HCV gene mutation in Lanzhou and the relationship with interferon-α induced immune response

目的探讨兰州地区丙型肝炎病毒(HCV)1b基因型5'非编码区(5'NCR)基因变异株的感染状态,及其与干扰素α疗效的关系。方法应用限制性内切酶酶切分析检测40例HCV 1b型中5'-NCR基因变异及9例干扰素α治疗患者中的5'-NCR基因变异。结果在40例HCV 1b型中存在5种感染状态:(1)有MboⅠ切点24/40(60.0%);(2)无MboⅠ切点变异株5/40(12.5%);(3)有MboⅠ和无MboⅠ切点混合感染株7/40(17.5%);(4)有BamHⅠ切点变异株2/40(5%);(5)有MboⅠ双切点变异株2/40(5%)。对9例干扰素α治疗的丙型肝炎患者血清进行5'-NCR变异株检测。5例干扰素α应答病例中,2例为2a型,3例为无MboⅠ切点的1b型。4例抗干扰素α病例中,1例为2a型,但在某节段存在着1b与2a混合状态,另3例为无MboⅠ。结论在丙型肝炎患者血清中存在单一的MboⅠ切点的样品,24/40(60.0%)可能是HCV野生株感染的状态。

Objective To study the relationship between gene mutation of 5＇ noncoding region（5＇NCR） of hepatitis C virus（HCV） genotype 1b in infection state and effect of interferon-alpha（IFNα） on the treatment of chronic hepatitis C.Methods Sera from 9 patients were collected before,during and after IFNα therapy and sera from 40 HCV 1b patients were collected.HCV 5＇NCR fragments were amplified from these samples by RT-PCR and sequenced by cutting with restriction endonuclease Mbo I and BamH I.Results There were 5 infection states in 40 patients with HCV 1b：（1） Mbo I restriction site was detected in 24 patients（24/40,60.0%）;（2） Mutation without Mbo I restriction site was detected in 5 patients（5/40,12.5%）;（3） 7 patients（7/40,17.5%） coinfected the strain with or without of Mbo I restriction site;（4）Mutation with BamH I restriction site was detected in 2 patients（2/40,0.5%）;（5） 2 patients（2/40,0.5%） presented with two Mbo I restriction sites.Then we checked the mutation of 5＇noncoding region of the sera from 9 patients with IFNα therapy.In the 5 patients with sustained virological response（SVR）,2 for HCV genotype 2a,3 for HCV genotype 1b without Mbo I restriction site.In the 4 patietns with nonresponder,1 for coinfection of HCV genotype 1b and 2a,3 for HCV genotype 1b without Mbo I restriction site.Conclusion Of 40 HCV genotype 1b serum samples,60.0% patients presented single Mbo I restriction site,suggesting the state of infection with wild type strain.