{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:33:22Z","timestamp":1792787602812,"version":"4.5.0"},"reference-count":75,"publisher":"American Society for Clinical Investigation","issue":"16","license":[{"start":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T00:00:00Z","timestamp":1755820800000},"content-version":"vor","delay-in-days":38,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R01AI164709"],"award-info":[{"award-number":["R01AI164709"]}]},{"name":"NIH","award":["R01CA228700"],"award-info":[{"award-number":["R01CA228700"]}]},{"name":"NIH","award":["R01DE033907"],"award-info":[{"award-number":["R01DE033907"]}]},{"name":"NIH","award":["U01CA275301"],"award-info":[{"award-number":["U01CA275301"]}]},{"name":"NIH","award":["R21AI181873"],"award-info":[{"award-number":["R21AI181873"]}]},{"name":"NIH","award":["R21AI170751"],"award-info":[{"award-number":["R21AI170751"]}]},{"name":"NIH","award":["P01CA269043"],"award-info":[{"award-number":["P01CA269043"]}]},{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"crossref","award":["PF-23-1144614-01-IBCD"],"award-info":[{"award-number":["PF-23-1144614-01-IBCD"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,8,22]]},"abstract":"<jats:p>\n                    X-linked Lymphoproliferative Syndromes (XLP), arising from mutations in\n                    <jats:italic>SH2D1A<\/jats:italic>\n                    or\n                    <jats:italic>XIAP<\/jats:italic>\n                    genes, are characterized by fulminant Epstein-Barr virus (EBV) infection. Lymphomas occur frequently in XLP-1 and in other congenital conditions with heightened EBV susceptibility, but not in XLP-2. Why XLP-2 patients are apparently protected from EBV-driven lymphomagenesis remains a key open question. To gain insights, newly EBV-infected versus receptor-stimulated primary B cells from XLP-2 patients or with\n                    <jats:italic>XIAP<\/jats:italic>\n                    CRISPR editing were compared with healthy controls.\n                    <jats:italic>XIAP<\/jats:italic>\n                    perturbation impeded outgrowth of newly EBV-infected B cells, but not of CD40 ligand and interleukin-21\u2013stimulated B cells. XLP-2\u2013deficient B cells showed significantly lower EBV transformation efficiency than cells from healthy controls. Interestingly, EBV-immortalized lymphoblastoid cell proliferation was not impaired by\n                    <jats:italic>XIAP<\/jats:italic>\n                    knockout, implicating a XIAP role in early EBV B cell transformation. Mechanistically, nascent EBV infection activated p53-mediated apoptosis signaling, which was counteracted by XIAP in control cells. With XIAP deficiency, EBV markedly elevated apoptosis rates over the first 2 weeks of infection. IFN-\u03b3, whose levels are increased with severe XLP2 EBV infection, markedly increased newly EBV-infected B cell apoptosis. These findings underscored XIAP\u2019s crucial role in support of the earliest stages of EBV-mediated B cell immortalization and provide insights into the curious absence of EBV\n                    <jats:sup>+<\/jats:sup>\n                    lymphoma in patients with XLP-2.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.193787","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T17:36:59Z","timestamp":1752773819000},"source":"Crossref","is-referenced-by-count":2,"title":["Insights into absence of lymphoma despite fulminant Epstein-Barr virus infection in patients with XIAP deficiency"],"prefix":"10.1172","volume":"10","author":[{"given":"Yizhe","family":"Sun","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Brigham and Women\u2019s Hospital, Boston, Massachusetts, USA."},{"name":"Center for Integrated Solutions for Infectious Diseases, Broad Institute, Cambridge, Massachusetts, 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