Composition and three-dimensional architecture of the dengue virus replication and assembly sites.

Composition and three-dimensional architecture of the dengue virus replication and assembly sites.
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DOI:
10.1016/j.chom.2009.03.007
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发表时间:
2009-04-23
影响因子:
30.3
通讯作者:
Bartenschlager R
Bartenschlager R
中科院分区:
医学1区
文献类型:
--
作者:
Welsch S;Miller S;Romero-Brey I;Merz A;Bleck CK;Walther P;Fuller SD;Antony C;Krijnse-Locker J;Bartenschlager R

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众所周知,正链RNA病毒会重新排列细胞膜,以促进病毒基因组的复制。这些膜的生物发生和三维组织以及复制和病毒组装位点之间的联系尚不完全清楚。利用电子显微镜,我们发现登革病毒(DENV)诱导的囊泡、卷曲膜和病毒颗粒是内质网(ER)衍生的,我们在病毒诱导的囊泡内检测到双链RNA,一种假定的RNA复制标记物。电子断层扫描(ET)显示denv诱导的膜结构是一个er衍生网络的一部分。此外,ET揭示了囊泡孔,可以释放新合成的病毒RNA,并揭示了DENV颗粒在直接与囊泡孔相对应的ER膜上的出芽。因此,DENV修饰内质网膜结构,以促进复制和有效地将基因组装入子代病毒。这种DENV复制和组装位点的结构可以解释黄病毒复制周期不同步骤的协调。
Positive-strand RNA viruses are known to rearrange cellular membranes to facilitate viral genome replication. The biogenesis and three-dimensional organization of these membranes and the link between replication and virus assembly sites is not fully clear. Using electron microscopy, we find Dengue virus (DENV)-induced vesicles, convoluted membranes, and virus particles to be endoplasmic reticulum (ER)-derived, and we detect double-stranded RNA, a presumed marker of RNA replication, inside virus-induced vesicles. Electron tomography (ET) shows DENV-induced membrane structures to be part of one ER-derived network. Furthermore, ET reveals vesicle pores that could enable release of newly synthesized viral RNA and reveals budding of DENV particles on ER membranes directly apposed to vesicle pores. Thus, DENV modifies ER membrane structure to promote replication and efficient encapsidation of the genome into progeny virus. This architecture of DENV replication and assembly sites could explain the coordination of distinct steps of the flavivirus replication cycle.
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