Three-dimensional analysis of budding sites and released virus suggests a revised model for HIV-1 morphogenesis.

Three-dimensional analysis of budding sites and released virus suggests a revised model for HIV-1 morphogenesis.
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DOI:
10.1016/j.chom.2008.10.013
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发表时间:
2008-12-11
影响因子:
30.3
通讯作者:
Kräusslich HG
Kräusslich HG
中科院分区:
医学1区
文献类型:
--
作者:
Carlson LA;Briggs JA;Glass B;Riches JD;Simon MN;Johnson MC;Müller B;Grünewald K;Kräusslich HG

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目前的HIV-1形态发生模型认为,新合成的病毒Gag多聚蛋白运输到细胞膜并在细胞膜上组装成球形蛋白壳。由此产生的后期出芽结构被认为是由细胞ESCRT机制切断将其连接到生产细胞的膜系链而释放的。使用电子断层扫描和扫描透射电子显微镜,我们发现,病毒粒子有一个形态和组成不同的晚出芽网站。在释放的病毒体中,Gag排列成一个连续但不完整的球体。与此相反,晚出芽网站缺乏功能ESCRT表现出一个几乎封闭的加格球。结果使我们提出,萌芽是由加格大会,但完成ESCRT依赖的方式之前,加格球是完整的。这表明ESCRT在HIV-1释放的早期起作用,类似于其在囊泡形成中的作用,并且不限于切断薄膜系链。
Current models of HIV-1 morphogenesis hold that newly synthesized viral Gag polyproteins traffic to and assemble at the cell membrane into spherical protein shells. The resulting late-budding structure is thought to be released by the cellular ESCRT machinery severing the membrane tether connecting it to the producer cell. Using electron tomography and scanning transmission electron microscopy, we find that virions have a morphology and composition distinct from late-budding sites. Gag is arranged as a continuous but incomplete sphere in the released virion. In contrast, late-budding sites lacking functional ESCRT exhibited a nearly closed Gag sphere. The results lead us to propose that budding is initiated by Gag assembly, but is completed in an ESCRT-dependent manner before the Gag sphere is complete. This suggests that ESCRT functions early in HIV-1 release—akin to its role in vesicle formation—and is not restricted to severing the thin membrane tether.
DOI: 10.1126/science.1161070
发表时间: 2008-09-05
期刊: Science (New York, N.Y.)
影响因子: --
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