{"doi":"10.1101/2024.09.19.613696","title":"Global remodeling of ADP-ribosylation by PARP1 suppresses influenza A virus infection","abstract":"ADP-ribosylation is a highly dynamic and fully reversible post-translational modification performed by poly(ADP-ribose) polymerases (PARPs) that modulates protein function, abundance, localization and turnover. Here we show that influenza A virus infection causes a rapid and dramatic upregulation of global ADP-ribosylation that inhibits viral replication. Mass spectrometry defined for the first time the global ADP-ribosylome during infection, creating an infection-specific profile with almost 4,300 modification sites on ~1,080 host proteins, as well as over 100 modification sites on viral proteins. Our data indicate that the global increase likely reflects a change in the form of ADP-ribosylation rather than modification of new targets. Functional assays demonstrated that modification of the viral replication machinery antagonizes its activity and further revealed that the anti-viral activity of PARPs and ADP-ribosylation is counteracted by the influenza A virus protein NS1, assigning a new activity to the primary viral antagonist of innate immunity. We identified PARP1 as the enzyme producing the majority of poly(ADP-ribose) present during infection. Influenza A virus replicated faster in cells lacking PARP1, linking PARP1 and ADP-ribosylation to the anti-viral phenotype. Together, these data establish ADP-ribosylation as an anti-viral innate immune-like response to viral infection antagonized by a previously unknown activity of NS1.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":486356,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9578,"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":491964,"name":"Isabel Uribe","orcid":"0000-0003-4092-3398","position":1,"is_corresponding":false},{"id":1330140,"name":"Kaitlin A. Davis","orcid":null,"position":2,"is_corresponding":false},{"id":344018,"name":"Robert Lyle McPherson","orcid":"0000-0002-5922-889X","position":3,"is_corresponding":false},{"id":1329770,"name":"Gloria P. Larson","orcid":"0000-0001-5836-1499","position":4,"is_corresponding":false},{"id":344020,"name":"Mohsen Badiee","orcid":"0000-0003-3722-4609","position":5,"is_corresponding":false},{"id":526986,"name":"Vy Anh Tran","orcid":"0000-0001-5533-8381","position":6,"is_corresponding":false},{"id":577948,"name":"Mitchell P. Ledwith","orcid":null,"position":7,"is_corresponding":false},{"id":1330141,"name":"Elizabeth M Feltman","orcid":null,"position":8,"is_corresponding":false},{"id":745152,"name":"Shuǐqìng Yú","orcid":"0000-0002-9473-566X","position":9,"is_corresponding":false},{"id":440220,"name":"Yíngyún Caì","orcid":"0000-0002-1101-0920","position":10,"is_corresponding":false},{"id":1330142,"name":"Che-Yuan Chang","orcid":null,"position":11,"is_corresponding":false},{"id":1330143,"name":"Xingyi Yang","orcid":null,"position":12,"is_corresponding":false},{"id":756322,"name":"Zhuo Ma","orcid":"0000-0002-9766-8239","position":13,"is_corresponding":false},{"id":206589,"name":"Paul Chang","orcid":null,"position":14,"is_corresponding":false},{"id":109882,"name":"Jens H. Kuhn","orcid":"0000-0002-7800-6045","position":15,"is_corresponding":false},{"id":236295,"name":"Anthony K. L. Leung","orcid":"0000-0001-5569-4036","position":16,"is_corresponding":false},{"id":481322,"name":"Andrew Mehle","orcid":"0000-0001-6060-4330","position":17,"is_corresponding":false},{"id":1329769,"name":"Zhenyu Zhang","orcid":"0000-0003-4974-1400","position":0,"is_corresponding":true}],"reference_count":93,"raw_metadata":null,"created_at":"2026-07-19T02:07:57.049469Z","pmid":"39345583","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":[]}