Cell-death-inducing DFFA-like Effector B Contributes to the Assembly of Hepatitis C Virus (HCV) Particles and Interacts with HCV NS5A.
Cell-death-inducing DFFA-like Effector B Contributes to the Assembly of Hepatitis C Virus (HCV) Particles and Interacts with HCV NS5A.
复制标题
诱导细胞死亡的 DFFA 样效应器 B 有助于丙型肝炎病毒 (HCV) 颗粒的组装并与 HCV NS5A 相互作用
DOI：
10.1038/srep27778
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发表时间：
2016-06-10
影响因子：
4.6
通讯作者：
Peng T
中科院分区：
文献类型：
--
作者：
Cai H;Yao W;Li L;Li X;Hu L;Mai R;Peng T
丙型肝炎病毒 (HCV) 使用极低密度脂蛋白 (VLDL) 途径的成分进行组装/释放。我们之前报道过肝细胞核因子4α（HNF4α）通过参与VLDL组装/分泌的下游因子参与HCV组装/释放。细胞死亡诱导 DFFA 样效应器 B (CIDEB) 是 VLDL 通路的重要调节因子。 CIDEB 是从细胞培养物 (HCVcc) 中进入 HCV 颗粒所必需的，但 CIDEB 对 HCV 生命周期进入后步骤的影响尚不清楚。在本研究中，我们确定除了 HCVcc 进入之外，CIDEB 也是 HCV 组装所必需的。此外，CIDEB与HCV NS5A蛋白相互作用，并且CIDEB的N末端和NS5A的结构域I参与了这种相互作用。此外，CIDEB 沉默会损害载脂蛋白 E (ApoE) 与 HCV 颗粒的关联。有趣的是，登革热病毒 (DENV) 生命周期的进入后阶段也需要 CIDEB。总的来说，这些结果表明 CIDEB 是一种参与 HCV 组装的新宿主因子，可能是通过与病毒蛋白相互作用，为 HCV 利用 VLDL 调节剂 CIDEB 提供了新的见解。
Hepatitis C virus (HCV) uses components of the very-low-density lipoprotein (VLDL) pathway for assembly/release. We previously reported that hepatocyte nuclear factor 4α (HNF4α) participates in HCV assembly/release through downstream factors those participate in VLDL assembly/secretion. Cell-death-inducing DFFA-like effector B (CIDEB) is an important regulator of the VLDL pathway. CIDEB is required for entry of HCV particles from cell culture (HCVcc), but the effects of CIDEB on the post-entry steps of the HCV lifecycle are unclear. In the present study, we determined that CIDEB is required for HCV assembly in addition to HCVcc entry. Furthermore, CIDEB interacts with the HCV NS5A protein, and the N terminus of CIDEB and the domain I of NS5A are involved in this interaction. Moreover, CIDEB silencing impairs the association of apolipoprotein E (ApoE) with HCV particles. Interestingly, CIDEB is also required for the post-entry stages of the dengue virus (DENV) life cycle. Collectively, these results indicate that CIDEB is a new host factor that is involved in HCV assembly, presumably by interacting with viral protein, providing new insight into the exploitation of the VLDL regulator CIDEB by HCV.