{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T22:36:12Z","timestamp":1791412572577,"version":"4.3.3"},"reference-count":119,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Kaposi\u2019s sarcoma-associated herpesvirus (KSHV) is a DNA virus linked to multiple malignancies associated with compromised immunity, such as Kaposi\u2019s sarcoma (KS) and primary effusion lymphoma (PEL). These malignancies are strongly linked to HIV coinfection and remain major oncogenic risks even with advanced antiretroviral therapy. Current treatments are limited and often non-curative, highlighting the need to define host pathways that constrain KSHV replication and tumor progression. STING (Stimulator of Interferon Genes) is an essential mediator of antiviral and antitumor immunity. STING has been shown to restrict KSHV reactivation in an artificial iSLK-based cell model, but further validation in more physiologically relevant models is needed. Moreover, STING\u2019s antitumor role has been widely evaluated in multiple types of cancer in clinical trials, but this remains poorly defined in KSHV-related cancers. In this study, we profiled multiple patient-derived PEL cell lines and found variable STING expression patterns. In comparison to the other PEL cells, BC3 had remarkably low STING expression. When stimulated with diABZI, a STING agonist, BCBL1\u2019s ability to reactivate from latency was robustly repressed by STING activation, reflected by attenuated viral gene transcription, protein expression, genome replication, and virion production. In contrast, the lytic reactivation status in BC3 was only minimally attenuated. Consistently, diABZI treatment restricted cell growth in multiple PEL cell lines, but BC3 showed minimal response. Additional loss- and gain-of-function experiments further supported an association between STING and reduced PEL cell growth, as H151 (STING inhibitor) increased BCBL1 growth whereas STING overexpression suppressed growth in both BCBL1 and BC3 cells. These data support STING pathway competence as an innate immune barrier for KSHV lytic reactivation and tumor progression. To assess the generalizability of STING\u2019s antitumor role, we utilized EBV-transformed lymphoblastoid cell lines (LCLs) with variable cGAS or STING protein levels. Consistently, the responsiveness of LCLs to diABZI aligned with STING pathway competence, with minimal effects on growth and viability when STING expression was low or deficient. Overall, this work links STING pathway competence to both antiviral control of KSHV reactivation and reduced lymphoma growth, suggesting a potential new approach to limit KSHV pathogenesis.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1823240","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T05:31:24Z","timestamp":1777959084000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["STING inhibits viral lytic reactivation and cell growth in primary effusion lymphoma"],"prefix":"10.3389","volume":"17","author":[{"given":"Tiffany S.","family":"Nelson","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida","place":["Gainesville, FL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathrine","family":"Pacini","sequence":"additional","affiliation":[{"name":"Department of Molecular 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