Carlson Lars-Anders, Briggs John A G, Glass Bärbel, Riches James D, Simon Martha N, Johnson Marc C, Müller Barbara, Grünewald Kay, Kräusslich Hans-Georg
Abteilung Virologie, Universitätsklinikum D-69120 Heidelberg, Germany.
Cell Host Microbe. 2008 Dec 11;4(6):592-9. doi: 10.1016/j.chom.2008.10.013.
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.
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其上组装成球形蛋白壳。由此产生的晚期出芽结构被认为是由细胞内体分选转运复合体（ESCRT）机制切断将其与产生病毒的细胞相连的膜系链而释放的。通过电子断层扫描和扫描透射电子显微镜，我们发现病毒粒子具有与晚期出芽位点不同的形态和组成。在释放的病毒粒子中，Gag排列成一个连续但不完整的球体。相比之下，缺乏功能性ESCRT的晚期出芽位点呈现出一个几乎封闭的Gag球体。这些结果使我们提出，出芽由Gag组装启动，但在Gag球体完整之前以ESCRT依赖的方式完成。这表明ESCRT在HIV-1释放的早期发挥作用——类似于其在囊泡形成中的作用——并且不限于切断细膜系链。
