title: LC3C Contributes to Vpu-Mediated Antagonism of BST2/Tetherin Restriction on HIV-1 Release through a Non-canonical Autophagy Pathway.
abstract: BST2 (bone marrow stromal antigen 2)/tetherin is a restriction factor of enveloped viruses, which blocks the release of viral particles. HIV-1 encodes proteins that antagonize this innate barrier, including the accessory protein Vpu. Here, we investigate whether the autophagy pathway and/or ATG proteins are hijacked by HIV-1 Vpu to circumvent BST2 restriction of viral release. We report that BST2 and Vpu are present in LC3-positive compartments. We found that Vpu selectively interacts with the ATG8 ortholog LC3C through the Vpu L63VEM66sequence. This sequence is required for Vpu to antagonize BST2 restriction. LC3C expression favors the removal of BST2 from the HIV-1 budding site, and thus HIV-1 release in BST2-expressing cells. Additionally, ATG5 and beclin 1/ATG6, but not all the components of the autophagy pathway, act with LC3C to facilitate Vpu antagonism of BST2 restriction. Altogether, our data support the view that a non-canonical autophagy pathway reminiscent of LC3-associated phagocytosis contributes to Vpu counteraction of BST2 restriction.
authors.affiliation: Inserm, U1016, Institut Cochin, 75014 Paris, France; Cnrs, UMR8104, 75014 Paris, France; University Paris Descartes, Sorbonne Paris Cité, 75014 Paris, France.
authors.forename: Ursula
authors.initials: U
authors.lastname: Madjo
authors.affiliation: Inserm, U1016, Institut Cochin, 75014 Paris, France; Cnrs, UMR8104, 75014 Paris, France; University Paris Descartes, Sorbonne Paris Cité, 75014 Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Leymarie
authors.affiliation: Inserm, U1016, Institut Cochin, 75014 Paris, France; Cnrs, UMR8104, 75014 Paris, France; University Paris Descartes, Sorbonne Paris Cité, 75014 Paris, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Frémont
authors.affiliation: Inserm, U1016, Institut Cochin, 75014 Paris, France; Cnrs, UMR8104, 75014 Paris, France; University Paris Descartes, Sorbonne Paris Cité, 75014 Paris, France.
authors.forename: Aurelia
authors.initials: A
authors.lastname: Kuster
authors.affiliation: Inserm, U1016, Institut Cochin, 75014 Paris, France; Cnrs, UMR8104, 75014 Paris, France; University Paris Descartes, Sorbonne Paris Cité, 75014 Paris, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Nehlich
authors.affiliation: Inserm, U1016, Institut Cochin, 75014 Paris, France; Cnrs, UMR8104, 75014 Paris, France; University Paris Descartes, Sorbonne Paris Cité, 75014 Paris, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Gallois-Montbrun
authors.affiliation: Inserm, U1016, Institut Cochin, 75014 Paris, France; Cnrs, UMR8104, 75014 Paris, France; University Paris Descartes, Sorbonne Paris Cité, 75014 Paris, France.
authors.forename: Katy
authors.initials: K
authors.lastname: Janvier
authors.affiliation: Inserm, U1016, Institut Cochin, 75014 Paris, France; Cnrs, UMR8104, 75014 Paris, France; University Paris Descartes, Sorbonne Paris Cité, 75014 Paris, France. Electronic address: clarisse.berlioz@inserm.fr.
authors.forename: Clarisse
authors.initials: C
authors.lastname: Berlioz-Torrent
mesh_terms: D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000378:metabolism*; D001343:Autophagy; D000071183:Autophagy-Related Proteins / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000378:metabolism; D057809:HEK293 Cells; D015497:HIV-1 / Q000378:metabolism*; D006367:HeLa Cells; D054298:Human Immunodeficiency Virus Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D011485:Protein Binding; D054334:Viral Regulatory and Accessory Proteins / Q000737:chemistry / Q000378:metabolism*; D057074:Virus Release; D000074010:Bone Marrow Stromal Antigen 2; D000086082:Viroporin Proteins
chemical_list: D015703:Antigens, CD; D000071183:Autophagy-Related Proteins; D058851:GPI-Linked Proteins; D054298:Human Immunodeficiency Virus Proteins; D008869:Microtubule-Associated Proteins; D054334:Viral Regulatory and Accessory Proteins; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C502071:MAP1LC3C protein, human; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins
keywords: ATG; ATG5; BST2; HIV-1; LC3-associated phagocytosis; LC3C; Vpu; autophagy; restriction; tetherin