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We show that treatment of an EBV\n            <jats:sup>+<\/jats:sup>\n            Burkitt's lymphoma cell line with 5-azacytidine led to a dose-dependent induction of EBV lytic antigen expression, including expression of the viral thymidine kinase (TK) and phosphotransferase (PT). Azacytidine treatment for 24 h modestly sensitized the cell line to all nucleosides tested. To better characterize EBV TK with regard to various nucleoside analogues, we expressed EBV TK in stable cell clones. Two EBV TK-expressing clones were moderately sensitive to high doses of acyclovir and penciclovir (PCV) (62.5 to 500 \u03bcM) and to lower doses of ganciclovir (GCV) and bromovinyldeoxyuridine (BVdU) (10 to 100 \u03bcM) compared to a control clone and were shown to phosphorylate GCV. Similar experiments in a transient overexpression system showed more killing of cells transfected with the EBV TK expression vector than of cells transfected with the control mutant vector (50 \u03bcM GCV for 4 days). A putative PT was also studied in the transient transfection system and appeared similar to the TK in phosphorylating GCV and conferring sensitivity to GCV, but not in BVdU- or PCV-mediated cell killing. Induction of EBV kinases in combination with agents such as GCV merits further evaluation as an alternative strategy to gene therapy for selective killing of EBV-infected cells.\n          <\/jats:p>","DOI":"10.1128\/aac.45.7.2082-2091.2001","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T10:06:42Z","timestamp":1027764402000},"page":"2082-2091","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":90,"title":["Induction of Epstein-Barr Virus Kinases To Sensitize Tumor Cells to Nucleoside Analogues"],"prefix":"10.1128","volume":"45","author":[{"given":"Stacy M.","family":"Moore","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Departments of Oncology1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer S.","family":"Cannon","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Departments of Oncology1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvette C.","family":"Tanhehco","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Departments of Oncology1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fayez M.","family":"Hamzeh","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Medicine,2 Johns Hopkins University School of Medicine, Baltimore, Maryland 21231"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard F.","family":"Ambinder","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Departments of Oncology1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.4.3284-3291.1999"},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","first-page":"6652","DOI":"10.1073\/pnas.88.15.6652","article-title":"A system for assaying homologous recombination at the endogenous human thymidine kinase gene.","volume":"88","author":"Benjamin M. 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