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ATG5 selectively engages virus-tethered BST2/tetherin in an LC3C-associated pathway

Bone marrow stromal antigen 2 (BST2)/tetherin is a restriction factor that reduces HIV-1 dissemination by tethering virus at the cell surface. BST2 also acts as a sensor of HIV-1 budding, establishing a cellular antiviral state. The HIV-1 Vpu protein antagonizes BST2 antiviral functions via multiple...

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Autores principales: Judith, Delphine, Versapuech, Margaux, Bejjani, Fabienne, Palaric, Marjory, Verlhac, Pauline, Kuster, Aurelia, Lepont, Leslie, Gallois-Montbrun, Sarah, Janvier, Katy, Berlioz-Torrent, Clarisse
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10193943/
https://www.ncbi.nlm.nih.gov/pubmed/37155854
http://dx.doi.org/10.1073/pnas.2217451120
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author Judith, Delphine
Versapuech, Margaux
Bejjani, Fabienne
Palaric, Marjory
Verlhac, Pauline
Kuster, Aurelia
Lepont, Leslie
Gallois-Montbrun, Sarah
Janvier, Katy
Berlioz-Torrent, Clarisse
author_facet Judith, Delphine
Versapuech, Margaux
Bejjani, Fabienne
Palaric, Marjory
Verlhac, Pauline
Kuster, Aurelia
Lepont, Leslie
Gallois-Montbrun, Sarah
Janvier, Katy
Berlioz-Torrent, Clarisse
author_sort Judith, Delphine
collection PubMed
description Bone marrow stromal antigen 2 (BST2)/tetherin is a restriction factor that reduces HIV-1 dissemination by tethering virus at the cell surface. BST2 also acts as a sensor of HIV-1 budding, establishing a cellular antiviral state. The HIV-1 Vpu protein antagonizes BST2 antiviral functions via multiple mechanisms, including the subversion of an LC3C-associated pathway, a key cell intrinsic antimicrobial mechanism. Here, we describe the first step of this viral-induced LC3C-associated process. This process is initiated at the plasma membrane through the recognition and internalization of virus-tethered BST2 by ATG5, an autophagy protein. ATG5 and BST2 assemble as a complex, independently of the viral protein Vpu and ahead of the recruitment of the ATG protein LC3C. The conjugation of ATG5 with ATG12 is dispensable for this interaction. ATG5 recognizes cysteine-linked homodimerized BST2 and specifically engages phosphorylated BST2 tethering viruses at the plasma membrane, in an LC3C-associated pathway. We also found that this LC3C-associated pathway is used by Vpu to attenuate the inflammatory responses mediated by virion retention. Overall, we highlight that by targeting BST2 tethering viruses, ATG5 acts as a signaling scaffold to trigger an LC3C-associated pathway induced by HIV-1 infection.
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spelling pubmed-101939432023-11-08 ATG5 selectively engages virus-tethered BST2/tetherin in an LC3C-associated pathway Judith, Delphine Versapuech, Margaux Bejjani, Fabienne Palaric, Marjory Verlhac, Pauline Kuster, Aurelia Lepont, Leslie Gallois-Montbrun, Sarah Janvier, Katy Berlioz-Torrent, Clarisse Proc Natl Acad Sci U S A Biological Sciences Bone marrow stromal antigen 2 (BST2)/tetherin is a restriction factor that reduces HIV-1 dissemination by tethering virus at the cell surface. BST2 also acts as a sensor of HIV-1 budding, establishing a cellular antiviral state. The HIV-1 Vpu protein antagonizes BST2 antiviral functions via multiple mechanisms, including the subversion of an LC3C-associated pathway, a key cell intrinsic antimicrobial mechanism. Here, we describe the first step of this viral-induced LC3C-associated process. This process is initiated at the plasma membrane through the recognition and internalization of virus-tethered BST2 by ATG5, an autophagy protein. ATG5 and BST2 assemble as a complex, independently of the viral protein Vpu and ahead of the recruitment of the ATG protein LC3C. The conjugation of ATG5 with ATG12 is dispensable for this interaction. ATG5 recognizes cysteine-linked homodimerized BST2 and specifically engages phosphorylated BST2 tethering viruses at the plasma membrane, in an LC3C-associated pathway. We also found that this LC3C-associated pathway is used by Vpu to attenuate the inflammatory responses mediated by virion retention. Overall, we highlight that by targeting BST2 tethering viruses, ATG5 acts as a signaling scaffold to trigger an LC3C-associated pathway induced by HIV-1 infection. National Academy of Sciences 2023-05-08 2023-05-16 /pmc/articles/PMC10193943/ /pubmed/37155854 http://dx.doi.org/10.1073/pnas.2217451120 Text en Copyright © 2023 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Biological Sciences
Judith, Delphine
Versapuech, Margaux
Bejjani, Fabienne
Palaric, Marjory
Verlhac, Pauline
Kuster, Aurelia
Lepont, Leslie
Gallois-Montbrun, Sarah
Janvier, Katy
Berlioz-Torrent, Clarisse
ATG5 selectively engages virus-tethered BST2/tetherin in an LC3C-associated pathway
title ATG5 selectively engages virus-tethered BST2/tetherin in an LC3C-associated pathway
title_full ATG5 selectively engages virus-tethered BST2/tetherin in an LC3C-associated pathway
title_fullStr ATG5 selectively engages virus-tethered BST2/tetherin in an LC3C-associated pathway
title_full_unstemmed ATG5 selectively engages virus-tethered BST2/tetherin in an LC3C-associated pathway
title_short ATG5 selectively engages virus-tethered BST2/tetherin in an LC3C-associated pathway
title_sort atg5 selectively engages virus-tethered bst2/tetherin in an lc3c-associated pathway
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10193943/
https://www.ncbi.nlm.nih.gov/pubmed/37155854
http://dx.doi.org/10.1073/pnas.2217451120
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