Trans-complemented hepatitis C virus particles as a versatile tool for study of virus assembly and infection
Trans-complemented hepatitis C virus particles as a versatile tool for study of virus assembly and infection
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DOI：
10.1016/j.virol.2012.05.033
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发表时间：
2012-10-10
期刊：
影响因子：
3.7
通讯作者：
Suzuki, Tetsuro
中科院分区：
文献类型：
--
作者：
Suzuki, Ryosuke;Saito, Kenji;Suzuki, Tetsuro
在这项研究中，我们比较了反式补体丙型肝炎病毒颗粒（HCVtcp）、细胞培养产生的HCV （HCVcc）和HCV假颗粒（HCVpp）的进入过程。抗cd81抗体将HCVtcp和HCVcc的进入量降低到接近背景水平，将HCVpp的进入量降低约50%。载脂蛋白e依赖感染在HCVtcp和HCVcc中被观察到，但在HCVpp中没有，这表明HCVtcp系统比HCVpp更适合作为HCV感染的模型。我们通过引入适应性突变和从亚基因组复制子结构中删除不需要复制的序列来提高HCVtcp的生产力。此外，HCVtcp在包装细胞中盲传导致NS3区N1586D发生新的突变，这有助于感染性病毒的组装。这些结果表明，我们基于质粒高效生产HCVtcp的系统有助于研究HCV生命周期，特别是病毒组装和感染。(C) 2012爱思唯尔公司版权所有。
In this study, we compared the entry processes of trans-complemented hepatitis C virus particles (HCVtcp), cell culture-produced HCV (HCVcc) and HCV pseudoparticles (HCVpp). Anti-CD81 antibody reduced the entry of HCVtcp and HCVcc to almost background levels, and that of HCVpp by approximately 50%. Apolipoprotein E-dependent infection was observed with HCVtcp and HCVcc, but not with HCVpp, suggesting that the HCVtcp system is more relevant as a model of HCV infection than HCVpp. We improved the productivity of HCVtcp by introducing adapted mutations and by deleting sequences not required for replication from the subgenomic replicon construct. Furthermore, blind passage of the HCVtcp in packaging cells resulted in a novel mutation in the NS3 region, N1586D, which contributed to assembly of infectious virus. These results demonstrate that our plasmid-based system for efficient production of HCVtcp is beneficial for studying HCV life cycles, particularly in viral assembly and infection. (C) 2012 Elsevier Inc. All rights reserved.