{"doi":"10.1021/acschembio.2c00176","title":"<i>S</i>-Palmitoylation and Sterol Interactions Mediate Antiviral Specificity of IFITMs","abstract":"Interferon-induced transmembrane proteins (IFITM1, 2, and 3) are important antiviral proteins that are active against many viruses, including influenza A virus (IAV), dengue virus (DENV), Ebola virus (EBOV), Zika virus (ZIKV), and severe acute respiratory syndrome coronavirus (SARS-CoV). IFITM proteins exhibit specificity in activity, but their distinct mechanisms of action and regulation are unclear. Since S-palmitoylation and cholesterol homeostasis are crucial for viral infections, we investigated IFITM interactions with cholesterol by photoaffinity cross-linking in mammalian cells along with molecular dynamic simulations and nuclear magnetic resonance analysis in vitro. These studies suggest that cholesterol can directly interact with S-palmitoylated IFITMs in cells and alter the conformation of IFITMs in membrane bilayers. Notably, we discovered that the S-palmitoylation levels regulate differential IFITM protein interactions with cholesterol in mammalian cells and specificity of antiviral activity toward IAV, SARS-CoV-2, and EBOV. Our studies suggest that modulation of IFITM S-palmitoylation levels and cholesterol interaction influence host susceptibility to different viruses.","journal":"ACS Chemical Biology","year":2022,"id":246326,"datarank":1.28735873053981,"base_score":3.713572066704308,"endowment":3.713572066704308,"self_citation_contribution":0.5570358100056463,"citation_network_contribution":0.7303229205341637,"self_endowment_contribution":0.5570358100056463,"citer_contribution":0.7303229205341637,"corpus_percentile":null,"corpus_rank":null,"citation_count":40,"citer_count":36,"citers_with_citation_signal":30,"citers_with_endowment":30,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9575,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":807930,"name":"Xinglin Yang","orcid":"0000-0002-1431-2836","position":1,"is_corresponding":false},{"id":565065,"name":"Hwa-Young Lee","orcid":"0000-0003-2332-1993","position":2,"is_corresponding":false},{"id":565064,"name":"Emma H. Garst","orcid":"0000-0001-8170-2343","position":3,"is_corresponding":false},{"id":807931,"name":"Estefania Valencia","orcid":"0009-0009-8362-0558","position":4,"is_corresponding":false},{"id":109548,"name":"Kartik Chandran","orcid":"0000-0003-0232-7077","position":5,"is_corresponding":false},{"id":56772,"name":"Wonpil Im","orcid":"0000-0001-5642-6041","position":6,"is_corresponding":false},{"id":376625,"name":"Howard C. Hang","orcid":"0000-0003-4053-5547","position":7,"is_corresponding":false},{"id":467624,"name":"Tandrila Das","orcid":"0000-0002-3398-9877","position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:23:43.438539Z","pmid":"35861660","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":[]}