A class II phosphoinositide 3-kinase plays an indispensable role in hepatitis C virus replication
A class II phosphoinositide 3-kinase plays an indispensable role in hepatitis C virus replication
复制标题
DOI：
10.1016/j.bbrc.2013.09.048
复制
发表时间：
2013-10-11
影响因子：
3.1
通讯作者：
Hanada, Kentaro
中科院分区：
文献类型：
--
作者：
Maehama, Tomohiko;Fukasawa, Masayoshi;Hanada, Kentaro
磷酸肌醇作为基本的信号分子，在多种细胞过程中发挥作用。某些类型的病毒可以利用宿主细胞磷酸肌醇信号系统来促进其复制周期。在这里，我们证明了β亚型II类PI 3 K（PI 3 K-C2 β）在丙型肝炎病毒（HCV）在人肝细胞癌细胞中的传播中起着不可或缺的作用。PI 3 K-C2 β的敲低消除了细胞中的HCV繁殖。使用HCV复制子系统，我们发现PI 3 K-C2 β的敲低基本上抑制了全基因组复制，同时显示出亚基因组复制的相对较小的减少，其中包括核心蛋白的结构蛋白被删除。我们还发现HCV核心蛋白对D4-磷酸化的磷酸肌醇具有结合活性，并且在细胞内与磷脂酰肌醇3，4-二磷酸重叠定位。这些结果表明，由PI 3 K-C2 β产生的磷酸肌醇通过与HCV核心蛋白结合在HCV复制周期中起着不可或缺的作用。(C)2013 Elsevier Inc. All rights reserved.
Phosphoinositides function as fundamental signaling molecules and play roles in diverse cellular processes. Certain types of viruses may employ host cell phosphoinositide signaling systems to facilitate their replication cycles. Here we demonstrate that the beta isoform of class II PI3K (PI3K-C2 beta) plays an indispensable role in hepatitis C virus (HCV) propagation in human hepatocellular carcinoma cells. Knockdown of PI3K-C2 beta abrogated HCV propagation in the cell. Using an HCV replicon system, we found that knockdown of PI3K-C2 beta substantially repressed the full-genome replication, while showing relatively small reductions in sub-genome replication, in which structural proteins including core protein were deleted. We also found that HCV core protein showed the binding activity towards D4-phosphorylated phosphoinositides and overlapped localization with phosphatidylinositol 3,4-bisphosphate in the cell. These results suggest that the phosphoinositide generated by PI3K-C2 beta plays an indispensable role in the HCV replication cycle through the binding to HCV core protein. (C) 2013 Elsevier Inc. All rights reserved.