Replicons from genotype 1b HCV-positive sera exhibit diverse sensitivities to anti-HCV reagents
Replicons from genotype 1b HCV-positive sera exhibit diverse sensitivities to anti-HCV reagents
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DOI：
10.1016/j.antiviral.2009.01.007
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发表时间：
2009-04-01
影响因子：
7.6
通讯作者：
Kato, Nobuyuki
中科院分区：
文献类型：
--
作者：
Nishimura, Go;Ikeda, Masanori;Kato, Nobuyuki
一半的1型丙型肝炎患者对目前的聚乙二醇化干扰素和利巴韦林治疗有抵抗力。对干扰素治疗的耐药性是一个紧迫的问题，特别是在感染I型丙型肝炎病毒的患者中。然而，丙型肝炎病毒株对包括干扰素在内的抗丙型肝炎病毒试剂的敏感性尚未得到彻底解决。在这里，除了我们先前建立的复制子(0株)外，我们还建立了三个不同的亚基因组复制子(1B-4、1B-5和KAH5株)。我们比较了四个复制子对干扰素-α、干扰素-γ、干扰素-λ、环孢素A和氟伐他汀的敏感性。在这些复制子中，1B-4和KAH5复制子对干扰素-lambda(EC50：1.50 ng/mlvs.8.50 ng/ml)和氟伐他汀(EC50：2.82mU/mlvs.7.87mU)最为敏感和耐药，尽管这些复制子在与0株的遗传距离、丙型肝炎病毒RNA表达水平以及对干扰素-α(EC50：1.44IU/mlvs.1.37IU/ml)和环孢素A(EC50：0.71mU/mlvs.0.96mU/ml)的敏感性方面具有相似的特征。因此，这些复制子是研究抗丙型肝炎病毒活性机制的有用工具，特别是在干扰素-lambda和他汀类药物中。(C)2009爱思唯尔B.V.保留所有权利。
Half of the population of genotype 1 HCV is resistant to current pegylated-interferon-alpha (PEG-IFN-alpha) and ribavirin therapy. The resistance to IFN therapy is an urgent problem, especially in patients with genotype I HCV infection. However, sensitivities among HCV strains to anti-HCV reagents including IFNs have not been thoroughly addressed. Here, we established three different subgenomic replicons (1B-4, 1B-5, and KAH5 strains) in addition to our previously established replicon (0 strain). We comparatively examined the sensitivities of four replicons to IFN-alpha, IFN-gamma, IFN-lambda, cyclosporine A, and fluvastatin. Among the replicons, the 1B-4 and KAH5 replicons were the most sensitive and resistant, respectively to IFN-lambda (EC50: 1.50 ng/ml vs. 8.50 ng/ml) and fluvastatin (EC50: 2.82 mu M vs. 7.87 mu M), although these replicons possessed similar features in terms of genetic distance from the 0 strain, HCV RNA expression levels, and sensitivity to IFN-alpha (EC50: 1.44 IU/ml vs. 1.37 IU/ml) and cyclosporine A (EC50: 0.71 mu g/ml vs. 0.96 mu g/ml). These replicons are thus useful tools for examining the mechanism of anti-HCV activity, especially in IFN-lambda and statins. (C) 2009 Elsevier B.V. All rights reserved.