{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T14:24:18Z","timestamp":1787667858974,"version":"build-2736575974"},"reference-count":37,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>A phase 1b\/2 study of the all\u2010oral \u201ckick\u2010and\u2010kill\u201d combo nanatinostat + valganciclovir (nana\u2010val) showed a\u2009~40% overall response rate in patients with relapsed\/refractory Epstein\u2010Barr virus (EBV)\u2010associated lymphomas. Despite the promising results in these difficult\u2010to\u2010treat cancers, there is little known about the effects of nanatinostat on EBV and cell death. In this work we demonstrate that nanatinostat, an HDAC1\/3 inhibitor, robustly induces the full EBV lytic cycle in a panel of EBV\u2010positive lymphoma and transformed cell lines (Burkitt, DLBCL, lymphoblastoid), spanning viral latency types and EBV genotypes. Nanatinostat drives lytic\u2010gene transcription across all kinetic classes, viral genome replication, and virion release, and kills cells at nanomolar concentrations. Although valganciclovir does not increase cytotoxicity, its ability to block viral DNA synthesis and virion production justifies its inclusion to prevent viral dissemination. Importantly, the two main metabolites of nanatinostat lack histone\u2010H3 acetylation activity and neither activate nor inhibit the EBV lytic phase, indicating that they are biologically inert with respect to EBV. These mechanistic insights clarify the clinical efficacy of nana\u2010val and support further development of kick\u2010and\u2010kill strategies for EBV\u2010driven malignancies.<\/jats:p>","DOI":"10.1002\/jmv.71077","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T11:20:16Z","timestamp":1785237616000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical\u2010Stage Nanatinostat Triggers Productive Epstein\u2010Barr Virus Lytic Replication"],"prefix":"10.1002","volume":"98","author":[{"given":"Ibukun A.","family":"Akinyemi","sequence":"first","affiliation":[{"name":"Child Health Research Institute, Department of Pediatrics University of Florida Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Travis M.","family":"Zeigler","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Pediatrics University of Florida Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Griffin H.","family":"Willman","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Pediatrics University of Florida Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devshree","family":"Patel","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Pediatrics University of Florida Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayman","family":"El\u2010Guindy","sequence":"additional","affiliation":[{"name":"Viracta Therapeutics Encinitas California USA"},{"name":"AbVir Therapeutics  California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael T.","family":"McIntosh","sequence":"additional","affiliation":[{"name":"Child Health Research Institute, Department of Pediatrics University of Florida 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