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Interferon resistance of hepatitis C virus

丙型肝炎病毒的干扰素抵抗

基本信息

批准号：
06670595
负责人：
CHAYAMA Kazuaki
金额：
$ 0.26万
依托单位：
Okinaka Memorial Institute for Medical Study
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670595/
关键词：
Hepatitis C virus amino acid sequence ISDR PCR C型肝炎ウイルスインターフェロン

项目摘要

Hepatitis C virus (HCV) genotype 1b and high pretreatment virus load are prdictive factors of poor response to interferon therapy in patients with chronic hepatitis C.However, few patients with low virus load and genotype 1b show poor response to treatment. To further examine the factors predicting the response to interferon therapy in patients with genotype 1b infection, we analyzed entire nucleotide sequences of HCV extracted from three non-responders and one responder. We were no able to identify any single amino acid mutation which determines the resitance to interferon. We also examined 57 consecutive patients who were treated with 624 million units of lymphoblastoid alpha-interferon. Multivariate analysis showed that pretreatment virus load and multiple amino acid substitutions in the ISDR significantly correlated with failure to eliminate the virus. Our data support the hypothesis that HCV without amino acid substitution in the ISDR is resistant to interferon treatment. However, polymerase chain reaction-based analysis of two responders with multiple amino acid substitutions in the ISDR revealed the presence of a small amount of wild type strain in their serum, suggesting that the wild type HCV is not resistant to interferon. The precise mechanism of anti-viral effect of interferon and its relationship with amino acid substitutions of the ISDR should be further investigated in order to develop a more effective anti-viral strategy.

丙型肝炎病毒（HCV）1b基因型和治疗前高病毒载量是慢性丙型肝炎患者对干扰素治疗反应不良的预测因素，但低病毒载量和1b基因型患者对干扰素治疗反应不良者较少。为了进一步研究预测基因型1b感染患者对干扰素治疗反应的因素，我们分析了从三个无应答者和一个应答者中提取的HCV的全核苷酸序列。我们不能确定任何一个决定干扰素耐药的氨基酸突变。我们还检查了57名连续患者，他们接受了6.24亿单位的淋巴母细胞α-干扰素治疗。多变量分析显示，预处理病毒载量和ISDR中的多个氨基酸取代与病毒消除失败显著相关。我们的数据支持这样的假设，即HCV在ISDR中没有氨基酸取代，对干扰素治疗有抗性。然而，基于聚合酶链反应的分析与ISDR中的多个氨基酸取代的两个响应者揭示了在他们的血清中存在少量的野生型株，这表明野生型HCV不耐干扰素。干扰素抗病毒作用的确切机制及其与ISDR氨基酸取代的关系有待进一步研究，以开发更有效的抗病毒策略。