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Despite advances in understanding EBV biology, targeted therapies for EBV-associated cancers remain limited. To identify novel dependencies in EBV-infected cancers, we performed genome-wide CRISPR-Cas9 loss-of-function screens in EBV+ lymphoblastoid versus Burkitt lymphoma cells, which differ by EBV latency programs. JunB emerged as a critical LCL-selective host dependency factor. LCL JunB knockout significantly decreased proliferation, with reduced G2\/M progression, but without inducing apoptosis. JunB was more highly expressed in B cells with the EBV latency III than latency I program and correlated with LMPist1 levels in newly infected B cells. LMP1 stimulated JunB expression in a manner dependent on its cytoplasmic tail TES1\/CTAR1 region and on canonical NF-\u03baB. EBV-activated JunB played an obligatory role in repression of the G1\/S phase inhibitor\n                  <jats:italic>CDKN2C<\/jats:italic>\n                  \/p18\n                  <jats:sup>INK4c<\/jats:sup>\n                  in LCLs but not Burkitt B cells. These findings establish an LMP1-JunB-p18\n                  <jats:sup>INK4c<\/jats:sup>\n                  axis as essential for EBV-driven lymphoblastoid B cell proliferation, suggest JunB-mediated cross-talk between Epstein-Barr nuclear antigens and LMP1, and highlight JunB as a potential therapeutic target for EBV-associated lymphoproliferative disorders.\n                <\/jats:p>","DOI":"10.64898\/2026.03.31.715635","type":"posted-content","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T13:10:14Z","timestamp":1775049014000},"source":"Crossref","is-referenced-by-count":0,"title":["CRISPR Screens Reveal Epstein-Barr Virus-activated JunB as a Key Lymphoblastoid B cell Dependency Factor that Represses Cyclin Dependent Kinase Inhibitor P18INK4c"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2432-2288","authenticated-orcid":false,"given":"Eric M.","family":"Burton","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Mass General Brigham Hospital, Boston, Massachusetts, United States of America"},{"name":"Center for Integrated Solutions for Infectious Diseases, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, United States of America"},{"name":"Department of Microbiology, Harvard Medical School, Boston, Massachusetts, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0081-9548","authenticated-orcid":false,"given":"Yifei","family":"Liao","sequence":"additional","affiliation":[{"name":"Center for Integrated Solutions for Infectious Diseases, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, United States of America"},{"name":"Department of Microbiology, Harvard Medical School, Boston, Massachusetts, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4216-1182","authenticated-orcid":false,"given":"Davide","family":"Maestri","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Mass General Brigham Hospital, Boston, Massachusetts, United States of America"},{"name":"Center for Integrated Solutions for Infectious Diseases, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, United States of America"},{"name":"Department of Microbiology, Harvard Medical School, Boston, Massachusetts, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bidisha","family":"Mitra","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Mass General Brigham Hospital, Boston, Massachusetts, United States of America"},{"name":"Center for Integrated Solutions for Infectious Diseases, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, United States of America"},{"name":"Department of Microbiology, Harvard Medical School, Boston, Massachusetts, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3965-3418","authenticated-orcid":false,"given":"Benjamin E.","family":"Gewurz","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Mass General Brigham Hospital, Boston, Massachusetts, United States of America"},{"name":"Center for Integrated Solutions for Infectious Diseases, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, United States of America"},{"name":"Department of Microbiology, Harvard Medical School, Boston, Massachusetts, United States of America"},{"name":"Program in Virology, Harvard Medical School, Boston, Massachusetts, United States of America;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026040408501258000_2026.03.31.715635v1.1","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-10-5765-6_5"},{"key":"2026040408501258000_2026.03.31.715635v1.2","doi-asserted-by":"publisher","DOI":"10.1111\/febs.16206"},{"key":"2026040408501258000_2026.03.31.715635v1.3","unstructured":"Gewurz BE , Longnecker R , Cohen JL. 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