{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T10:56:13Z","timestamp":1788432973837,"version":"build-2803163510"},"reference-count":81,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T00:00:00Z","timestamp":1750723200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Peer Reviewed Cancer Research Program","award":["CA220188"],"award-info":[{"award-number":["CA220188"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>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\u2013Barr 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.<\/jats:p>","DOI":"10.3390\/v17070885","type":"journal-article","created":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T10:44:41Z","timestamp":1750761881000},"page":"885","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["IRF4 Mediates Immune Evasion to Facilitate EBV Transformation"],"prefix":"10.3390","volume":"17","author":[{"given":"Ling","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA"},{"name":"Center of Excellence for Inflammation, Infectious Diseases and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Culton R.","family":"Hensley","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7051-8984","authenticated-orcid":false,"given":"Jahan","family":"Rifat","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam D.","family":"Walker","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharine","family":"Ning","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan P.","family":"Moorman","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA"},{"name":"Center of Excellence for Inflammation, Infectious Diseases and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA"},{"name":"Hepatitis (HCV\/HIV) Program, James H. Quillen VA Medical Center, Johnson City, TN 37614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi Q.","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA"},{"name":"Center of Excellence for Inflammation, Infectious Diseases and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA"},{"name":"Hepatitis (HCV\/HIV) Program, James H. 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