Cell culture-adaptive NS3 mutations required for the robust replication of genome-length hepatitis C virus RNA
Cell culture-adaptive NS3 mutations required for the robust replication of genome-length hepatitis C virus RNA
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DOI：
10.1016/j.virusres.2006.12.011
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发表时间：
2007-04-01
期刊：
影响因子：
5
通讯作者：
Kato, Nobuyuki
中科院分区：
文献类型：
--
作者：
Abe, Ken-ichi;Ikeda, Masanori;Kato, Nobuyuki
我们最近利用来自SO细胞的治愈细胞建立了一个基因组长度的HCVRNA复制细胞系(1b型O株；这里称为O细胞)，其中复制了带有适应性NS5A突变的丙型肝炎病毒亚基因组复制子RNA(S2200R)。O细胞的特征揭示了第二个适应性NS3突变(K1609E)，这是基因组长度的丙型肝炎病毒RNA复制所必需的。为了阐明适应性突变在基因组长度的丙型肝炎病毒RNA复制中的作用，我们新建立了一种和三种基因组长度的丙型肝炎病毒RNA复制细胞系，分别具有SO和0细胞的细胞背景，并发现了更多的适应性突变(Q11 12R，P1115L和E1202G)，这是基因组长度的丙型肝炎病毒RNA复制所必需的。我们进一步发现，适应性NS3突变的特定组合显著增强了丙型肝炎病毒RNA的复制，而不考虑所研究的细胞系。这些发现表明，特定的病毒因素可能会影响基因组长度的丙型肝炎病毒RNA的复制水平。(C)2006爱思唯尔B.V.保留所有权利。
We recently established a genome-length HCV RNA-replicating cell line (O strain of genotype 1b; here called O cells) using cured cells derived from sO cells, in which HCV subgenomic replicon RNA with an adaptive NS5A mutation (S2200R) is replicated. Characterization of the O cells revealed a second adaptive NS3 mutation (K1609E) required for genome-length HCV RNA replication. To clarify the role of adaptive mutation in genome-length HCV RNA replication, we newly established one and three kinds of genome-length HCV RNA-replicating cell lines possessing the cell background of so and 0 cells, respectively, and found additional adaptive NS3 mutations (Q11 12R, P1115L, and E1202G) required for the robust replication of genome-length HCV RNA. We further found that specific combinations of adaptive NS3 mutations drastically enhanced HCV RNA replication, regardless of the cell lines examined. These findings suggest that specific viral factors may affect the replication level of genome-length HCV RNA. (c) 2006 Elsevier B.V. All rights reserved.