Hepatitis C virus p7 and NS2 proteins are essential for production of infectious virus
Hepatitis C virus p7 and NS2 proteins are essential for production of infectious virus
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DOI：
10.1128/jvi.00690-07
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发表时间：
2007-08-01
影响因子：
5.4
通讯作者：
Rice, Charles M.
中科院分区：
文献类型：
--
作者：
Jones, Christopher T.;Murray, Catherine L.;Rice, Charles M.
丙型肝炎病毒（HCV）感染是一个全球性的健康问题，影响估计3%的世界人口。最近，已经建立了细胞培养系统，首次允许再现完整的病毒生命周期。由于预测HCV蛋白p7和NS 2不是病毒体的主要成分，也不是RNA复制所需的，因此我们研究了它们是否可能在病毒生命周期中具有其他作用。在这里，我们利用最近描述的传染性J6/JFH嵌合体，以建立p7和NS 2蛋白是必要的HCV感染性。此外，该活性不需要未加工形式的p7和NS 2。两个保守的碱性残基的突变，以前被证明是重要的离子通道活性的p7在体外，大大削弱了感染性病毒的生产。NS 2的蛋白酶结构域是感染性所必需的，而其催化活性位点则是p53。我们的结论是，p7和NS 2的功能在病毒形态发生的早期阶段，在组装的感染性病毒。
Hepatitis C virus (HCV) infection is a global health concern affecting an estimated 3% of the world's population. Recently, cell culture systems have been established, allowing recapitulation of the complete virus life cycle for the first time. Since the HCV proteins p7 and NS2 are not predicted to be major components of the virion, nor are they required for RNA replication, we investigated whether they might have other roles in the viral life cycle. Here we utilize the recently described infectious J6/JFH chimera to establish that the p7 and NS2 proteins are essential for HCV infectivity. Furthermore, unprocessed forms of p7 and NS2 were not required for this activity. Mutation of two conserved basic residues, previously shown to be important for the ion channel activity of p7 in vitro, drastically impaired infectious virus production. The protease domain of NS2 was required for infectivity, whereas its catalytic active site was dispensable. We conclude that p7 and NS2 function at an early stage of virion morphogenesis, prior to the assembly of infectious virus.