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...

Full description

Saved in:
Bibliographic Details
Published inProceedings of the National Academy of Sciences - PNAS Vol. 120; no. 20; p. 1
Main Authors Judith, Delphine, Versapuech, Margaux, Bejjani, Fabienne, Palaric, Marjory, Verlhac, Pauline, Kuster, Aurelia, Lepont, Leslie, Gallois-Montbrun, Sarah, Janvier, Katy, Berlioz-Torrent, Clarisse
Format Journal Article
LanguageEnglish
Published Washington National Academy of Sciences 16.05.2023
Subjects
Antigens
Antiviral state
Autophagy
Bone marrow
Cell surface
Conjugation
HIV
Human immunodeficiency virus
Inflammation
Internalization
Membranes
Proteins
Tethering
Virions
Viruses
Vpu protein
Online AccessGet full text

Cover

More Information
Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.221745112