{"doi":"10.1073/pnas.2217451120","title":"ATG5 selectively engages virus-tethered BST2/tetherin in an LC3C-associated pathway","abstract":"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.","journal":"Proceedings of the National Academy of Sciences","year":2023,"id":339689,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9522,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":322114,"name":"Margaux Versapuech","orcid":null,"position":1,"is_corresponding":false},{"id":893719,"name":"Fabienne Bejjani","orcid":"0000-0002-1392-1410","position":2,"is_corresponding":false},{"id":1073659,"name":"Marjory Palaric","orcid":"0009-0000-2955-7468","position":3,"is_corresponding":false},{"id":639021,"name":"Pauline Verlhac","orcid":"0000-0002-1059-4645","position":4,"is_corresponding":false},{"id":1074159,"name":"Aurélia Kuster","orcid":null,"position":5,"is_corresponding":false},{"id":1074160,"name":"Leslie Lepont","orcid":null,"position":6,"is_corresponding":false},{"id":321017,"name":"Sarah Gallois‐Montbrun","orcid":"0000-0002-7870-1814","position":7,"is_corresponding":false},{"id":1073660,"name":"Katy Janvier","orcid":"0000-0002-3105-4736","position":8,"is_corresponding":false},{"id":321015,"name":"Clarisse Berlioz‐Torrent","orcid":"0000-0002-5782-8154","position":9,"is_corresponding":false},{"id":1073658,"name":"Delphine Judith","orcid":"0000-0003-2098-4812","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-19T01:10:49.535464Z","pmid":"37155854","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}