{"doi":"10.1371/journal.pbio.3002696","title":"SAMD9L acts as an antiviral factor against HIV-1 and primate lentiviruses by restricting viral and cellular translation","abstract":"Sterile alpha motif domain-containing proteins 9 and 9-like (SAMD9/9L) are associated with life-threatening genetic diseases in humans and are restriction factors of poxviruses. Yet, their cellular function and the extent of their antiviral role are poorly known. Here, we found that interferon-stimulated human SAMD9L restricts HIV-1 in the late phases of replication, at the posttranscriptional and prematuration steps, impacting viral translation and, possibly, endosomal trafficking. Surprisingly, the paralog SAMD9 exerted an opposite effect, enhancing HIV-1. More broadly, we showed that SAMD9L restricts primate lentiviruses, but not a gammaretrovirus (MLV), nor 2 RNA viruses (arenavirus MOPV and rhabdovirus VSV). Using structural modeling and mutagenesis of SAMD9L, we identified a conserved Schlafen-like active site necessary for HIV-1 restriction by human and a rodent SAMD9L. By testing a gain-of-function constitutively active variant from patients with SAMD9L-associated autoinflammatory disease, we determined that SAMD9L pathogenic functions also depend on the Schlafen-like active site. Finally, we found that the constitutively active SAMD9L strongly inhibited HIV, MLV, and, to a lesser extent, MOPV. This suggests that the virus-specific effect of SAMD9L may involve its differential activation/sensing and the virus ability to evade from SAMD9L restriction. Overall, our study identifies SAMD9L as an HIV-1 antiviral factor from the cell autonomous immunity and deciphers host determinants underlying the translational repression. This provides novel links and therapeutic avenues against viral infections and genetic diseases.","journal":"PLoS Biology","year":2024,"id":426961,"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":0.9631,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":883895,"name":"Clara Dahoui","orcid":null,"position":1,"is_corresponding":false},{"id":883210,"name":"Clément de la Myre Mory","orcid":"0000-0003-4302-1365","position":2,"is_corresponding":false},{"id":1180278,"name":"Kodie Noy","orcid":null,"position":3,"is_corresponding":false},{"id":1180279,"name":"Laura Guiguettaz","orcid":null,"position":4,"is_corresponding":false},{"id":322114,"name":"Margaux Versapuech","orcid":null,"position":5,"is_corresponding":false},{"id":1180277,"name":"Clara Loyer","orcid":null,"position":6,"is_corresponding":false},{"id":1180066,"name":"M. Pillon","orcid":"0000-0003-0736-3288","position":7,"is_corresponding":false},{"id":1180280,"name":"Mégane Wcislo","orcid":null,"position":8,"is_corresponding":false},{"id":988610,"name":"Laurent Guéguen","orcid":"0000-0001-7838-791X","position":9,"is_corresponding":false},{"id":321015,"name":"Clarisse Berlioz‐Torrent","orcid":"0000-0002-5782-8154","position":10,"is_corresponding":false},{"id":767956,"name":"Andrea Cimarelli","orcid":"0000-0003-0892-0488","position":11,"is_corresponding":false},{"id":392684,"name":"Mathieu Mateo","orcid":"0000-0001-7941-0245","position":12,"is_corresponding":false},{"id":1180067,"name":"Francesca Fiorini","orcid":"0000-0001-8388-1576","position":13,"is_corresponding":false},{"id":297825,"name":"Emiliano P. Ricci","orcid":"0000-0002-9789-5837","position":14,"is_corresponding":false},{"id":883214,"name":"Lucie Etienne","orcid":"0000-0002-8585-7534","position":15,"is_corresponding":false},{"id":1180065,"name":"Alexandre Legrand","orcid":"0000-0002-9587-8208","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-07-19T01:58:42.796720Z","pmid":"38959200","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":[]}