{"doi":"10.1093/jleuko/qiaf150","title":"The macrocyclic peptide rhesus theta defensin 1 activates interferon and antiviral pathways in human monocytes","abstract":"Rhesus theta defensin (RTD)-1, a cyclic antimicrobial peptide, regulates gene expression and immune signaling pathways in cell culture and animal models of immune-mediated diseases. In lipopolysaccharide-stimulated cells, RTD-1 inhibition of proinflammatory cytokine secretion and gene expression is mediated through inhibition of the NF-κB and MAP kinase signaling pathways. To gain insights into RTD-1 regulation of naïve cells, we performed RNA sequencing (RNA-seq) to determine the effect of the peptide on global gene expression in human monocytes and THP-1 monocytes. In both cell types, analysis of differentially expressed genes revealed stimulation of interferon and antiviral gene expression pathways. RTD-1 induced Y701 phosphorylation of STAT1 and activated the ISRE reporter in a JAK-dependent manner. Stimulation of the ISRE reporter by RTD-1 was interferon-α/β receptor dependent but was independent of its NF-κB inhibitory activity in lipopolysaccharide-stimulated cells. RTD-1 inhibited infection of vesicular stomatitis virus pseudotyped with G glycoprotein or SARS-CoV-2 spike protein in THP-1 and Vero E6 cells, respectively. RTD-1 also inhibited infection of Calu-3 2B4 cells by SARS-CoV-2 virus, demonstrating antiviral activity of RTD-1 in diverse cell types. These results demonstrate that RTD-1 stimulates interferon and antiviral pathways, potentially priming cells for resistance to viral infection.","journal":"Journal of Leukocyte Biology","year":2025,"id":579183,"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":0.9563,"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":1070891,"name":"Katie Trinh","orcid":"0000-0002-5695-305X","position":1,"is_corresponding":false},{"id":1489821,"name":"Jill E Henley","orcid":null,"position":2,"is_corresponding":false},{"id":876051,"name":"Philip Sell","orcid":"0009-0009-8636-5628","position":3,"is_corresponding":false},{"id":1489822,"name":"Vyoma Thakker","orcid":null,"position":4,"is_corresponding":false},{"id":747359,"name":"André J. Ouellette","orcid":"0000-0002-7987-5779","position":5,"is_corresponding":false},{"id":1129190,"name":"Michael E. Selsted","orcid":"0000-0002-7152-4739","position":6,"is_corresponding":false},{"id":1129189,"name":"Prasad Tongaonkar","orcid":"0009-0001-2112-6919","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-19T02:58:30.282164Z","pmid":"41139211","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":[]}