Construction and characterization of infectious hepatitis C virus chimera containing structural proteins directly from genotype 1b clinical isolates
Construction and characterization of infectious hepatitis C virus chimera containing structural proteins directly from genotype 1b clinical isolates
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含有直接来自基因型 1b 临床分离株的结构蛋白的传染性丙型肝炎病毒嵌合体的构建和表征
DOI：
10.1016/j.virol.2013.04.030
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发表时间：
2013-08-15
期刊：
影响因子：
3.7
通讯作者：
Zhong, Jin
中科院分区：
文献类型：
--
作者：
Lu, Jie;Tao, Wanyin;Zhong, Jin
HCV基因型是临床结果的主要决定因素，GT1b HCV感染是最难治疗的，也是东亚和欧洲的主要基因型。我们直接从GT1b临床分离株中开发了含有结构基因（Core、El、E2）、p7和NS2的1stTMD的1b/JFH-1基因型间重组体。通过克隆选择策略，从3例GT1b患者血清中获得4个功能克隆，可在Huh7.5.1细胞中产生感染性病毒。通过序列传代和反向遗传对恢复的病毒进行测序分析，发现gt1b起源区域的适应性突变足以增强传染性。E2和患者原始血清单克隆抗体能有效阻断其中3种病毒（26C3mt、52B6mt和79L9），而对26C6mt病毒无明显抑制作用。1b/JFH-1嵌合病毒的可用性将对分离特异性中和的研究和抗病毒治疗的评估具有重要意义。(C) 2013爱思唯尔公司版权所有。
HCV genotype is a major determinant of clinical outcome, and GT1b HCV infection is the most difficult to treat and also the predominant genotype in East Asia and Europe. We developed 1b/JFH-1 intergenotypic recombinants containing the structural genes (Core, El, E2), p7 and the 1stTMD of NS2 directly from GT1b clinical isolates. Through a cloning selection strategy, we obtained 4 functional clones from 3 cases of GT1b patients' sera, which could produce infectious viruses in Huh7.5.1 cells. Sequencing analysis of recovered viruses from serial passage and reverse genetics revealed that adaptive mutations in the GT1b-originated region were enough for the enhancement of infectivity. A monoclonal antibody to E2 and original patient sera could efficiently block 3 of the viruses (26C3mt, 52B6mt and 79L9) while had little effect on 26C6mt viruses. The availability of 1b/JFH-1 chimeric viruses will be important for studies of isolate-specific neutralization and useful in evaluating antiviral therapies. (C) 2013 Elsevier Inc. All rights reserved.