Internal initiation of translation efficiency in different hepatitis C genotypes isolated from interferon treated patients

作     者：Sáiz, JC Lopez de Quinto, S Ibarrola, N López-Labrador, FX Sánchez-Tapias, JM Rodés, J Martínez-Salas, E 

作者机构：Univ Autonoma Madrid CSIC Ctr Biol Mol Severo Ochoa E-28049 Madrid Spain Univ Barcelona Hosp Clin IDIBAPS Dept MedLiver Unit Barcelona Spain 

出 版 物：《ARCHIVES OF VIROLOGY》 (病毒学文献)

年 卷 期：1999年第144卷第2期

页      面：215-229页

核心收录：

学科分类：0710[理学-生物学] 1007[医学-药学(可授医学、理学学位)] 100705[医学-微生物与生化药学] 07[理学] 071005[理学-微生物学] 10[医学] 

主　　题：抗病毒药/治疗应用 碱基序列 结合部位 COS细胞 细胞系 氯霉素O-乙酰转移酶/遗传学 氯霉素O-乙酰转移酶/代谢 DNA 互补/化学 DNA 互补/遗传学 基因表达调控 基因型 HeLa细胞 肝炎病毒属/药物作用 肝炎病毒属/遗传学 肝炎病毒属/分离和提纯 肝炎 丙型/治疗 干扰素类/治疗应用 萤光素酶类/遗传学 萤光素酶类/代谢 分子序列数据 肽链起始 翻译 蛋白质生物合成/遗传学 RNA 病毒/遗传学 RNA 病毒/代谢 重组融合蛋白质类/遗传学 重组融合蛋白质类/代谢 逆转录聚合酶链反应 核糖体/代谢 序列比对 序列分析 DNA 序列同源性 核酸 肿瘤细胞 培养的 变异(遗传学) 成年人 动物 女(雌)性 人类 男(雄)性 中年人 

摘      要：Initiation of translation of hepatitis C viral RNA occurs internally and it is mediated by a segment of about 330 nucleotides termed Internal Ribosome Entry Site (IRES) located in the 5 end region. While being the most conserved part of the genome, this region also accumulates nucleotide substitutions which are often covariant. In this study we have examined the activity and sequence variation of IRES elements belonging to genotypes 1b, 2a/2c and 3a in patients that responded or not to interferon therapy. The substitutions found in the IRES region analyzed were predicted to maintain the secondary structure of the RNA. Comparison of their efficiency to promote internal initiation of translation in bicistronic constructs supported the conclusion that for both Ib and 3a genotypes, response to interferon therapy and IRES activity are unrelated, although sequence homology was not always found among isolates from patients with different type of response. IRES activity of the studied genotypes varied about 4-fold under the conditions used in our in vivo assays depending on the cell line used for transfection. Such differences were not evidenced in vitro suggesting that the differences observed depend on trans-acting factors present in the transfected cell.