Cellular and viral determinants of the hepatitis C virus replication and assembly compartment (13)

丙型肝炎病毒（HCV）复制周期的一个标志是细胞内膜的广泛重组，导致主要由双膜囊泡（DMV）组成的复制细胞器（RO）的形成。在上一个资助期内，我们能够从HCV感染的细胞中纯化DMV，获得NS4B病毒孔蛋白样活性的证据，并提出了DMV生物发生的模型。在第三个资助期内，我们的目标是通过破译不同的脂质和蛋白质因子在DMV生物发生和感染性HCV颗粒组装中的作用来验证所提出的模型。此外，我们想证实和表征NS4B病毒孔蛋白的活性及其在HCV复制中的作用。

A hallmark of the hepatitis C virus (HCV) replication cycle is the extensive reorganization of intracellular membranes leading to the formation of replication organelles (ROs) mainly consisting of double-membrane vesicles (DMVs). Within the last funding period we were able to purify DMVs from HCV-infected cells, obtained evidence for a viroporin-like activity of NS4B and proposed a model on DMV biogenesis. Within the third funding period we aim to verify the proposed model by deciphering the role of distinct lipids and proteinaceous factors in DMV biogenesis and the assembly of infectious HCV particles. In addition we want to corroborate and characterize NS4B viroporin activity and its role in HCV replication.