{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:36:56Z","timestamp":1791196616749,"version":"4.1.0"},"reference-count":74,"publisher":"American Society for Microbiology","issue":"14","license":[{"start":{"date-parts":[[2013,7,15]],"date-time":"2013-07-15T00:00:00Z","timestamp":1373846400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2013,7,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The latent-to-lytic switch of Epstein-Barr virus (EBV) is mediated by the immediate early protein BZLF1 (Z). However, the cellular factors regulating this process remain incompletely characterized. In this report, we show that the B-cell-specific transcription factor Pax5 helps to promote viral latency in B cells by blocking Z function. Although Z was previously shown to directly interact with Pax5 and inhibit its activity, the effect of Pax5 on Z function has not been investigated. Here, we demonstrate that Pax5 inhibits Z-mediated lytic viral gene expression and the release of infectious viral particles in latently infected epithelial cell lines. Conversely, we found that shRNA-mediated knockdown of endogenous Pax5 in a Burkitt lymphoma B-cell line leads to viral reactivation. Furthermore, we show that Pax5 reduces Z activation of early lytic viral promoters in reporter gene assays and inhibits Z binding to lytic viral promoters\n            <jats:italic>in vivo<\/jats:italic>\n            . We confirm that Pax5 and Z directly interact and show that this interaction requires the carboxy-terminal DNA-binding\/dimerization domain of Z and the amino-terminal DNA-binding domain of Pax5. A Pax5 DNA-binding mutant (V26G\/P80R) that interacts with Z retains the ability to inhibit Z function, whereas a Pax5 mutant (\u0394106-110) that is deficient for interaction with Z does not inhibit Z-mediated lytic viral reactivation. Since the B-cell-specific transcription factor Oct-2 also directly interacts with Z and inhibits its function, these results suggest that EBV uses multiple redundant mechanisms to establish and maintain viral latency in B cells.\n          <\/jats:p>","DOI":"10.1128\/jvi.00546-13","type":"journal-article","created":{"date-parts":[[2013,5,16]],"date-time":"2013-05-16T03:32:49Z","timestamp":1368675169000},"page":"8053-8063","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":38,"title":["The B-Cell-Specific Transcription Factor and Master Regulator Pax5 Promotes Epstein-Barr Virus Latency by Negatively Regulating the Viral Immediate Early Protein BZLF1"],"prefix":"10.1128","volume":"87","author":[{"given":"Ryan M.","family":"Raver","sequence":"first","affiliation":[{"name":"Departments of Oncology (McArdle Laboratory for Cancer Research), University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA"},{"name":"Cellular and Molecular Pathology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda R.","family":"Panfil","sequence":"additional","affiliation":[{"name":"Departments of Oncology (McArdle Laboratory for Cancer Research), University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA"},{"name":"Cellular and Molecular Biology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacy R.","family":"Hagemeier","sequence":"additional","affiliation":[{"name":"Departments of Oncology (McArdle Laboratory for Cancer Research), University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon C.","family":"Kenney","sequence":"additional","affiliation":[{"name":"Departments of Oncology (McArdle Laboratory for Cancer Research), University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA"},{"name":"Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"2603","volume-title":"Fields virology","author":"Kieff E","year":"2007","unstructured":"KieffE RickinsonAB. 2007. 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