论文部分内容阅读
目的研究ＨＣＶ基因组的变异与干扰素治疗应答的关系以及干扰素治疗后患者体内病毒株的改变和变异。方法８例慢性丙型肝炎患者给予干扰素治疗，于治疗前及治疗后采集患者血清，扩增其血清中ＨＣＶ非结构基因５ｂ（ＮＳ５ｂ）区ｃＤＮＡ，克隆后，每例患者挑取６个克隆，测定重组子中ＮＳ５ｂｃＤＮＡ序列。结果４例患者在治疗后血清中ＨＣＶ阴性，为干扰素反应组，另４例于治疗中、治疗后血清中ＨＣＶＲＮＡ持续阳性，为非反应组。治疗前，反应组４例患者血清中分别含有１、１、１及３株ＨＣＶ，而非反应组４例患者血清中分别含有４、５、６及６株ＨＣＶ。与ＨＣ－Ｃ２或ＨＣ－Ｊ６相比，患者血清中ＨＣＶ的误义突变与无义突变之比在反应组为（１７．６１～３０．９５）％间，在非反应组为（３３．１１～７６．４７）％。治疗后，非反应组４例患者中，分别有２、３、４及４株ＨＣＶ被清除，各有２株ＨＣＶ存留于血清中。平均氨基酸变异数在消失病毒株与存留的病毒株中分别为４．３～５．５与５．５～９．０。有２株存留的病毒株在治疗后发生了突变，１株于２７２４位由甘氨酸突变为精氨酸，２７４２位由缬氨酸突变为丙氨酸。结论ＨＣＶ在准种及核苷酸水平上的变异均影响干扰素治疗的效果。干扰素治疗中?
Objective To study the relationship between HCV genomic variation and IFN response and the alteration and variation of viral strains in patients after interferon treatment. Methods Eight patients with chronic hepatitis C were treated with interferon. Serum was collected before and after treatment, and the cDNA of non-structural gene 5b (NS5b) of HCV was amplified. After cloning, 6 clones The NS5b cDNA sequence in the recombinant was assayed. Results Serum HCV was negative in 4 patients after treatment, which was interferon response group. In the other 4 patients, HCVRNA in serum was continuously positive after treatment, which was non-response group. Before treatment, four patients in the reaction group contained 1, 1, 1 and 3 HCV strains, respectively, while 4 patients in the non-reaction group contained 4, 5, 6 and 6 HCV strains respectively. Compared with HC-C2 or HC-J6, the ratio of HCV missense mutation and nonsense mutation in patients’ sera was (17.61 ~ 30.95)% in patients and non-responders (33.11 ~ 76.47)%. After treatment, 2, 4, 4, and 4 HCVs were eliminated from the 4 non-responders, and 2 HCVs remained in the serum. The average number of amino acid variation in the disappearance of the virus strains and surviving strains were 4.3 to 5.5 and 5.5 to 9.0. Two strains survived mutations after treatment, one at 2724 from glycine to arginine, 2742 from valine to alanine. Conclusion The variations of HCV in quasispecies and nucleotides all affect the effect of interferon treatment. Interferon treatment?