the escrt-0 component hrs is required for hiv-1 vpu-mediated bst-2tetherin down-regulation所需的小时escrt-0组件是hiv - 1 vpu-mediated bst-2tetherin下调.pdfVIP

The ESCRT-0 Component HRS is Required for HIV-1 Vpu-Mediated BST-2/Tetherin Down-Regulation 1,2 3 1,2 1,2 3 Katy Janvier *, Annegret Pelchen–Matthews , Jean-Baptiste Renaud , Marina Caillet , Mark Marsh , Clarisse Berlioz-Torrent1,2¤* ´ 1 Institut Cochin, Universite Paris Descartes, CNRS (UMR 8104), Paris, France, 2 INSERM, U1016, Paris, France, 3 Cell Biology Unit, MRC Laboratory for Molecular Cell Biology, University College London, London, United Kingdom Abstract The Endosomal Sorting Complexes Required for Transport (ESCRT) machinery, a highly conserved set of four hetero- oligomeric protein complexes, is required for multivesicular body formation, sorting ubiquitinylated membrane proteins for lysosomal degradation, cytokinesis and the final stages of assembly of a number of enveloped viruses, including the human immunodeficiency viruses. Here, we show an additional role for the ESCRT machinery in HIV-1 release. BST-2/tetherin is a restriction factor that impedes HIV release by tethering mature virus particles to the plasma membrane. We found that HRS, a key component of the ESCRT-0 complex, promotes efficient release of HIV-1 and that siRNA-mediated HRS depletion induces a BST-2/tetherin phenotype. This activity is related to the ability of the HIV-1 Vpu protein to down-regulate BST-2/ tetherin. We found that BST-2/tetherin undergoes constitutive ESCRT-dependent sorting for lysosomal degradation and that this degradation is enhanced by Vpu expression. We demonstrate that Vpu-mediated BST-2/tetherin down-modulation and degradation require HRS (ESCRT-0) function and that knock down of HRS increases cellular levels of