Sequential biogenesis of host cell membrane rearrangements induced by hepatitis C virus infection.

Sequential biogenesis of host cell membrane rearrangements induced by hepatitis C virus infection.
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DOI:
10.1007/s00018-012-1213-0
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发表时间:
2013-04
期刊:
Cellular and molecular life sciences : CMLS
影响因子:
--
通讯作者:
Roingeard P
Roingeard P
中科院分区:
其他
文献类型:
--
作者:
Ferraris P;Beaumont E;Uzbekov R;Brand D;Gaillard J;Blanchard E;Roingeard P

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与大多数正链RNA病毒一样,丙型肝炎病毒(HCV)形成由复制RNA、病毒和锚定在改变的细胞膜上的宿主蛋白组成的膜相关复制复合物。我们使用定性和定量电子显微镜(EM),免疫EM,和3D重建系列EM切片的组合来分析HCV诱导的宿主细胞膜改变。观察到三种不同类型的膜改变:簇状囊泡(ViC)、连续囊泡(CV)和双膜囊泡(DMV)。感染早期观察到的主要超微结构变化是脂质滴周围CV网络的形成。感染周期的后期阶段的特征是DMV数量大幅增加,这可能来自CV。这些DMV被认为构成了携带病毒复制复合物的膜结构,其中病毒复制牢固且永久地建立,并保护病毒免受双链RNA触发的宿主抗病毒应答。本文的在线版本(doi:10.1007/s 00018 -012-1213-0)包含补充材料,可供授权用户使用。
Like most positive-strand RNA viruses, hepatitis C virus (HCV) forms a membrane-associated replication complex consisting of replicating RNA, viral and host proteins anchored to altered cell membranes. We used a combination of qualitative and quantitative electron microscopy (EM), immuno-EM, and the 3D reconstruction of serial EM sections to analyze the host cell membrane alterations induced by HCV. Three different types of membrane alteration were observed: vesicles in clusters (ViCs), contiguous vesicles (CVs), and double-membrane vesicles (DMVs). The main ultrastructural change observed early in infection was the formation of a network of CVs surrounding the lipid droplets. Later stages in the infectious cycle were characterized by a large increase in the number of DMVs, which may be derived from the CVs. These DMVs are thought to constitute the membranous structures harboring the viral replication complexes in which viral replication is firmly and permanently established and to protect the virus against double-stranded RNA-triggered host antiviral responses. The online version of this article (doi:10.1007/s00018-012-1213-0) contains supplementary material, which is available to authorized users.