CD317/Tetherin Is Enriched in the HIV-1 Envelope and Downregulated from the Plasma Membrane upon Virus Infection
CD317/Tetherin Is Enriched in the HIV-1 Envelope and Downregulated from the Plasma Membrane upon Virus Infection
复制标题
DOI：
10.1128/jvi.02421-09
复制
发表时间：
2010-05-01
影响因子：
5.4
通讯作者：
Kraeusslich, Hans-Georg
中科院分区：
文献类型：
--
作者：
Habermann, Anja;Krijnse-Locker, Jacomine;Kraeusslich, Hans-Georg
CD 317/Bst-2/tetherin是一种宿主因子，通过在某些生产细胞的质膜上捕获病毒体来限制人类免疫缺陷病毒1型（HIV-1）的释放。它被HIV-1辅助蛋白Vpu拮抗。先前的光学显微镜研究将CD 317定位于质膜和内体区室，并显示Vpu诱导下调。在本研究中，我们进行了定量免疫电镜CD 317在细胞生产野生型或Vpu缺陷型HIV-1和对照细胞。双标记实验表明，CD 317定位于质膜，早期和回收内体，和trans-Golgi网络。HIV-1感染后，CD 317大量迁移到内体，这种作用部分被Vpu抵消。出乎意料的是，与各自的质膜相比，CD 317在病毒芽和细胞相关和无细胞病毒的膜中富集，并且这种富集不依赖于Vpu。这些结果表明，CD 317的拴系活性关键取决于其在细胞表面的密度，似乎受其在病毒体膜中的密度的影响较小。
CD317/Bst-2/tetherin is a host factor that restricts the release of human immunodeficiency virus type 1 (HIV-1) by trapping virions at the plasma membrane of certain producer cells. It is antagonized by the HIV-1 accessory protein Vpu. Previous light microscopy studies localized CD317 to the plasma membrane and the endosomal compartment and showed Vpu induced downregulation. In the present study, we performed quantitative immunoelectron microscopy of CD317 in cells producing wild-type or Vpu-defective HIV-1 and in control cells. Double-labeling experiments revealed that CD317 localizes to the plasma membrane, to early and recycling endosomes, and to the trans-Golgi network. CD317 largely relocated to endosomes upon HIV-1 infection, and this effect was partly counteracted by Vpu. Unexpectedly, CD317 was enriched in the membrane of viral buds and cell-associated and cell-free viruses compared to the respective plasma membrane, and this enrichment was independent of Vpu. These results suggest that the tethering activity of CD317 critically depends on its density at the cell surface and appears to be less affected by its density in the virion membrane.