{"doi":"10.1101/2025.06.30.662398","title":"The aryl hydrocarbon receptor interacting protein suppresses RNA virus-induced type I IFN and IL-6 in mouse macrophages","abstract":"Abstract Aryl hydrocarbon receptor (AhR) interacting protein (AIP) suppresses type I IFN production by interacting with and preventing the nuclear translocation of the transcription factor IRF7. The kinase TBK1 phosphorylates AIP to promote IRF7 binding and the inhibition of the type I interferon (IFN) response. However, it is unknown if AIP expression in innate immune cells is important to suppress type I IFN in the context of RNA virus infection in vitro and in vivo . In this study we generated myeloid cell-specific AIP conditional knockout mice ( Aip fl/fl xLysM-Cre) to investigate AIP regulation of innate immune signaling in myeloid cells. Bone marrow-derived macrophages (BMDMs) from Aip fl/fl xLysM-Cre mice had diminished viral replication and increased production of IFNα/b and IL-6 in response to RNA virus infection. AIP-deficient macrophages exhibited increased IRF7 expression and impaired virus-induced IRF7 degradation. AIP interacted with the E3 ubiquitin ligase SOCS1 and enhanced SOCS1 stability and its interaction with IRF7 to promote the proteasomal degradation of IRF7. Aip fl/fl xLysM-Cre mice exhibited improved survival upon influenza A virus (IAV) infection compared to control mice. Together, these results indicate that myeloid cell-specific AIP suppresses the innate immune response by targeting IRF7.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":569576,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9551,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":513889,"name":"Todd M. Umstead","orcid":"0009-0004-4112-711X","position":1,"is_corresponding":false},{"id":788944,"name":"Zissis C. Chroneos","orcid":"0000-0002-9841-7917","position":2,"is_corresponding":false},{"id":277005,"name":"Edward W. Harhaj","orcid":"0000-0003-1197-6765","position":3,"is_corresponding":false},{"id":1096952,"name":"Sarah A. Kazzaz","orcid":"0000-0003-0362-9499","position":0,"is_corresponding":true}],"reference_count":31,"raw_metadata":null,"created_at":"2026-07-19T02:56:59.652443Z","pmid":"40631146","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":[]}