The ESCRT-0 component HRS is required for HIV-1 Vpu-mediated BST-2/tetherin down-regulation.

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 assemb...

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Main Authors: Katy Janvier, Annegret Pelchen-Matthews, Jean-Baptiste Renaud, Marina Caillet, Mark Marsh, Clarisse Berlioz-Torrent
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-02-01
Series:PLoS Pathogens
Online Access:https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1001265&type=printable
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author Katy Janvier
Annegret Pelchen-Matthews
Jean-Baptiste Renaud
Marina Caillet
Mark Marsh
Clarisse Berlioz-Torrent
author_facet Katy Janvier
Annegret Pelchen-Matthews
Jean-Baptiste Renaud
Marina Caillet
Mark Marsh
Clarisse Berlioz-Torrent
author_sort Katy Janvier
collection DOAJ
description 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 BST-2/tetherin and restricts virus release. Furthermore, HRS co-precipitates with Vpu and BST-2. Our results provide further insight into the mechanism by which Vpu counteracts BST-2/tetherin and promotes HIV-1 dissemination, and they highlight an additional role for the ESCRT machinery in virus release.
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spelling doaj-art-6c690e0cc83f4f2584fe72df89b9e5212025-08-20T02:34:16ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742011-02-0172e100126510.1371/journal.ppat.1001265The ESCRT-0 component HRS is required for HIV-1 Vpu-mediated BST-2/tetherin down-regulation.Katy JanvierAnnegret Pelchen-MatthewsJean-Baptiste RenaudMarina CailletMark MarshClarisse Berlioz-TorrentThe 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 BST-2/tetherin and restricts virus release. Furthermore, HRS co-precipitates with Vpu and BST-2. Our results provide further insight into the mechanism by which Vpu counteracts BST-2/tetherin and promotes HIV-1 dissemination, and they highlight an additional role for the ESCRT machinery in virus release.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1001265&type=printable
spellingShingle Katy Janvier
Annegret Pelchen-Matthews
Jean-Baptiste Renaud
Marina Caillet
Mark Marsh
Clarisse Berlioz-Torrent
The ESCRT-0 component HRS is required for HIV-1 Vpu-mediated BST-2/tetherin down-regulation.
PLoS Pathogens
title The ESCRT-0 component HRS is required for HIV-1 Vpu-mediated BST-2/tetherin down-regulation.
title_full The ESCRT-0 component HRS is required for HIV-1 Vpu-mediated BST-2/tetherin down-regulation.
title_fullStr The ESCRT-0 component HRS is required for HIV-1 Vpu-mediated BST-2/tetherin down-regulation.
title_full_unstemmed The ESCRT-0 component HRS is required for HIV-1 Vpu-mediated BST-2/tetherin down-regulation.
title_short The ESCRT-0 component HRS is required for HIV-1 Vpu-mediated BST-2/tetherin down-regulation.
title_sort escrt 0 component hrs is required for hiv 1 vpu mediated bst 2 tetherin down regulation
url https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1001265&type=printable
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