Department of Pediatrics and Department of Microbiology and Immunology, Emory University, Atlanta, Georgia, USA.
PLoS Pathog. 2010 Feb 5;6(2):e1000749. doi: 10.1371/journal.ppat.1000749.
Tetherin/BST2 was identified in 2008 as the cellular factor responsible for restricting HIV-1 replication at a very late stage in the lifecycle. Tetherin acts to retain virion particles on the plasma membrane after budding has been completed. Infected cells that express large amounts of tetherin display large strings of HIV virions that remain attached to the plasma membrane. Vpu is an HIV-1 accessory protein that specifically counteracts the restriction to virus release contributed by tetherin. Tetherin is an unusual Type II transmembrane protein that contains a GPI anchor at its C-terminus and is found in lipid rafts. The leading model for the mechanism of action of tetherin is that it functions as a direct physical tether bridging virions and the plasma membrane. However, evidence that tetherin functions as a physical tether has thus far been indirect. Here we demonstrate by biochemical and immunoelectron microscopic methods that endogenous tetherin is present on the viral particle and forms a bridge between virion particles and the plasma membrane. Endogenous tetherin was found on HIV particles that were released by partial proteolytic digestion. Immunoelectron microscopy performed on HIV-infected T cells demonstrated that tetherin forms an apparent physical link between virions and connects patches of virions to the plasma membrane. Linear filamentous strands that were highly enriched in tetherin bridged the space between some virions. We conclude that tetherin is the physical tether linking HIV-1 virions and the plasma membrane. The presence of filaments with which multiple molecules of tetherin interact in connecting virion particles is strongly suggested by the morphologic evidence.
Tetherin/BST2 于 2008 年被鉴定为一种细胞因子，负责在生命周期的晚期限制 HIV-1 的复制。Tetherin 作用于在出芽完成后将病毒粒子保留在质膜上。表达大量 tetherin 的感染细胞显示出与质膜相连的 HIV 病毒粒子的长串。Vpu 是一种 HIV-1 辅助蛋白，它专门抵消 tetherin 对病毒释放的限制。Tetherin 是一种不寻常的 II 型跨膜蛋白，其 C 末端含有 GPI 锚，存在于脂筏中。tetherin 作用机制的主导模型是它作为连接病毒粒子和质膜的直接物理连接物。然而，到目前为止，tetherin 作为物理连接物的功能证据都是间接的。在这里，我们通过生化和免疫电子显微镜方法证明，内源性 tetherin 存在于病毒粒子上，并在病毒粒子和质膜之间形成桥。内源性 tetherin 存在于通过部分蛋白水解消化释放的 HIV 粒子上。在感染 HIV 的 T 细胞上进行的免疫电子显微镜显示，tetherin 在病毒粒子之间形成明显的物理连接，并将病毒粒子连接到质膜上。高度富含 tetherin 的线性丝状链桥接了一些病毒粒子之间的空间。我们得出结论，tetherin 是连接 HIV-1 病毒粒子和质膜的物理连接物。形态学证据强烈表明，存在与连接病毒粒子的多个 tetherin 分子相互作用的丝状结构。
