丙型肝炎病毒非结构基因5b的变异及与干扰素治疗的关系  

Variation in hepatitis C virus NS 5b nucleotide sequence and its relationship with interferon treatment

作　　者：魏来[1] 杜绍财[1] 王豪[1] 孙焱[1] 陶其敏[1] 冯百芳[1] 

机构地区：[1]北京医科大学人民医院肝病研究所

出　　处：《中华实验和临床病毒学杂志》1997年第3期223-226,共4页Chinese Journal of Experimental and Clinical Virology

基　　金：国家八五攻关及CMB部分资助

摘　　要：以聚合酶链反应直接序列分析方法测定了４例无症状慢性丙型肝炎病毒（ＨＣＶ）感染者，与９例接受干扰素治疗的慢性丙型肝炎患者血清中ＨＣＶ非结构基因５ｂ（ＮＳ５ｂ）ｃＤＮＡ的序列。发现，与已发表的Ⅱ／１ｂ型ＨＣＶ序列相比，无症状慢性ＨＣＶ感染者的ＨＣＶ在核苷酸水平的同源性高于干扰素治疗有效的慢性丙型肝炎患者（９５．６５％±２．６１％比９４．３５％±２．２９％），后者又高于干扰素治疗无效的慢性丙型肝炎患者（９２．７０％±１．９０％）。还发现在干扰素治疗后，治疗无效者血清中ＨＣＶＮＳ５ｂｃＤＮＡ序列发生明显变化，在所测定的３８０个核苷酸中有９～４８个发生碱基替换，从而导致所编码的氨基酸中有６～２０个发生突变。结果提示，ＨＣＶＮＳ５ｂ基因变异与病情及干扰素治疗有一定关系。变异较大者常出现明显的临床表现，且干扰素治疗可能趋势于失败。In order to investigate variation in hepatitis C virus (HCV) nonstructural 5b (NS5b) nucleotide sequence and the relationship with interferon treatment, cDNA containing in this region were obtained by reverse transcription polymerase chain reaction from the sera of 4 HCV RNA positive asymptomatic chronic carriers and 9 chronic hepatitis C patients. The cDNA were then directly analysed by polymerase chain reaction directed sequencing. Compared with three published HCV type Ⅱ/1b sequences (HCV J, HC C2 and HCV BDS), the homology of HCV was lower in the patients with chronic hepatitis C (93.52%±2.09% average), especially in nonresponders to interferon (92.70±1.90% average), than in asymptomatic HCV carriers (95.65±2.61%). In 5 patients, HCV RNA was eliminated by interferon treatment. In the remaining 4 interferon-treated HCV survived patients there were 9-48 nucleotide substitutions in HCV mutants out of 380 nucleotides, resulting 6-20 amino acids changes out of 126 amino acids. These results suggested that NS5b region variants play an important role in maintaining persistent infection and the evolution of NS5b is associated with the effect of interferon treatment.

关 键 词：丙型肝炎病毒 病毒变异 干扰素 丙型肝炎 

分 类 号：R512.630.5[医药卫生—内科学]