ATG5 selectively engages virus-tethered BST2/tetherin in an LC3C-associated pathway.
Delphine JudithMargaux VersapuechFabienne BejjaniMarjory PalaricPauline VerlhacAurelia KusterLeslie LepontSarah Gallois-MontbrunKaty JanvierClarisse Berlioz-TorrentPublished in: Proceedings of the National Academy of Sciences of the United States of America (2023)
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.
Keyphrases
- simultaneous determination
- antiretroviral therapy
- bone marrow
- hiv positive
- human immunodeficiency virus
- hiv infected
- mass spectrometry
- hepatitis c virus
- hiv testing
- hiv aids
- sars cov
- amino acid
- binding protein
- oxidative stress
- cell surface
- mesenchymal stem cells
- protein protein
- men who have sex with men
- diabetic rats
- genetic diversity