{"doi":"10.3390/v17070885","title":"IRF4 Mediates Immune Evasion to Facilitate EBV Transformation","abstract":"The lymphocyte-specific transcription factor interferon regulatory factor 4 (IRF4) is a key player in immune evasion in cancers, with the complex mechanism(s) being barely understood. In this study, we have focused on the role of IRF4 in regulating T cell functions through its transcriptional regulation of programmed death 1 (PD1) and its ligand PD1 ligand 1 (PD-L1), which were identified as IRF4 transcriptional targets in multi-omics analysis. We have shown that IRF4 transcriptionally regulates both PD1 and PD-L1, promoting immune suppression in the context of Epstein-Barr virus (EBV) infection. Co-culturing EBV+ JiJoye lymphoma cells with CD4+ T cells or with peripheral blood mononuclear cells (PBMCs) downregulates CD4+ T cell functions, but the depletion of IRF4 in EBV+ JiJoye lymphoma cells reduces PD1 and PD-L1 expression, and partially restores CD4+ T cell functions. Moreover, CD4+ T cell depletion from PBMCs enhances EBV transformation, and EBV has a greater efficiency in transforming PBMCs from HIV patients with impaired CD4+ T cell functions. These findings support the role of IRF4 in immune evasion by upregulating PD1/PD-L1 during EBV transformation, and that functional CD4+ T cells are essential for limiting EBV transformation.","journal":"Viruses","year":2025,"id":544951,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9606,"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":750471,"name":"Culton R. Hensley","orcid":null,"position":1,"is_corresponding":false},{"id":1435841,"name":"Jahan Rifat","orcid":null,"position":2,"is_corresponding":false},{"id":1435407,"name":"Adam D. Walker","orcid":"0000-0003-3754-838X","position":3,"is_corresponding":false},{"id":1138704,"name":"Katharine Ning","orcid":null,"position":4,"is_corresponding":false},{"id":336323,"name":"Jonathan P. Moorman","orcid":"0000-0002-6102-6541","position":5,"is_corresponding":false},{"id":664839,"name":"Zhi Q. Yao","orcid":"0000-0002-1333-1007","position":6,"is_corresponding":false},{"id":336322,"name":"Shunbin Ning","orcid":"0000-0001-5484-5779","position":7,"is_corresponding":false},{"id":681760,"name":"Ling Wang","orcid":"0000-0003-3220-6065","position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":null,"created_at":"2026-07-19T02:53:17.418915Z","pmid":"40733503","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":[]}