Live-cell visualization of dynamics of HIV budding site interactions with an ESCRT component
Live-cell visualization of dynamics of HIV budding site interactions with an ESCRT component
复制标题
DOI：
10.1038/ncb2215
复制
发表时间：
2011-04-01
影响因子：
21.3
通讯作者：
Lamb, Don C.
中科院分区：
文献类型：
--
作者：
Baumgaertel, Viola;Ivanchenko, Sergey;Lamb, Don C.
HIV（人类免疫缺陷病毒）转移细胞ESCRT（运输所需的内体分选复合物）机制以促进病毒体从感染细胞释放。ESCRT由四种异聚复合物（ESCRT-0至ESCRT-III）组成，它们介导不同的膜破裂过程，最重要的是在多泡体处形成腔内囊泡。ATP酶VPS 4（vacuolar protein sorting 4）在ESCRT功能的晚期发挥作用，为ESCRT解离提供能量。招募ESCRT的后期结构域基序在病毒的Gag多蛋白和ESCRT在HIV释放的作用是牢固确立的，但事件的顺序，其动力学和作用机制的个别ESCRT组件在HIV出芽目前尚不清楚。使用活细胞成像，我们显示VPS 4A在宿主细胞质膜上向新生HIV颗粒的后期结构域依赖性募集。VPS 4A的募集是短暂的，导致至少2至5个VPS 4十二聚体在HIV出芽位点组装的单个或几个爆发。爆发持续了类似35？s，并在颗粒释放前出现可变延迟。这些结果表明VPS 4A在导致HIV-1释放的膜断裂中具有直接作用。
HIV (human immunodeficiency virus) diverts the cellular ESCRT (endosomal sorting complex required for transport) machinery to promote virion release from infected cells. The ESCRT consists of four heteromeric complexes (ESCRT-0 to ESCRT-III), which mediate different membrane abscission processes, most importantly formation of intralumenal vesicles at multivesicular bodies. The ATPase VPS4 (vacuolar protein sorting 4) acts at a late stage of ESCRT function, providing energy for ESCRT dissociation. Recruitment of ESCRT by late-domain motifs in the viral Gag polyprotein and a role of ESCRT in HIV release are firmly established, but the order of events, their kinetics and the mechanism of action of individual ESCRT components in HIV budding are unclear at present. Using live-cell imaging, we show late-domain-dependent recruitment of VPS4A to nascent HIV particles at the host cell plasma membrane. Recruitment of VPS4A was transient, resulting in a single or a few bursts of at least two to five VPS4 dodecamers assembling at HIV budding sites. Bursts lasted for similar to 35?s and appeared with variable delay before particle release. These results indicate that VPS4A has a direct role in membrane scission leading to HIV-1 release.