{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T14:56:39Z","timestamp":1780584999933,"version":"3.54.1"},"update-to":[{"DOI":"10.1371\/journal.ppat.1014211","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000}}],"reference-count":99,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NCI","award":["CA16038"],"award-info":[{"award-number":["CA16038"]}]},{"name":"NCI","award":["CA12055"],"award-info":[{"award-number":["CA12055"]}]},{"DOI":"10.13039\/100000057","name":"NIGMS","doi-asserted-by":"crossref","award":["T32 GM07223"],"award-info":[{"award-number":["T32 GM07223"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100030442","name":"The Anna Fuller Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100030442","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NCI","award":["CA275310"],"award-info":[{"award-number":["CA275310"]}]},{"name":"NCI","award":["CA275310"],"award-info":[{"award-number":["CA275310"]}]},{"DOI":"10.13039\/100000072","name":"NIDCR","doi-asserted-by":"crossref","award":["DE034654"],"award-info":[{"award-number":["DE034654"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000072","name":"NIDCR","doi-asserted-by":"crossref","award":["DE034654"],"award-info":[{"award-number":["DE034654"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000072","name":"NIDCR","doi-asserted-by":"crossref","award":["DE032623"],"award-info":[{"award-number":["DE032623"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000072","name":"NIDCR","doi-asserted-by":"crossref","award":["DE032623"],"award-info":[{"award-number":["DE032623"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100018268","name":"Children\u2019s Miracle Network Hospitals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018268","name":"Children\u2019s Miracle Network Hospitals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009168","name":"Animal and Plant Health Inspection Service","doi-asserted-by":"publisher","award":["6000027242"],"award-info":[{"award-number":["6000027242"]}],"id":[{"id":"10.13039\/100009168","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Epstein-Barr virus (EBV), an oncogenic virus, actively remodels the intracellular environment during its lytic (replicative\/productive) phase to facilitate genome replication, virion packaging, and egress while attempting to evade immune responses. A key aspect of this remodeling is the downregulation of host gene expression, a phenomenon known as host shutoff. This process is prominently mediated by the EBV-encoded nuclease\n                    <jats:italic>BGLF5<\/jats:italic>\n                    , but\n                    <jats:italic>BGLF5<\/jats:italic>\n                    -independent mechanisms also contribute \u2013 most notably, the viral lytic switch protein ZEBRA, which can suppress host protein synthesis. Despite this broad suppression, the expression of certain host genes essential for lytic progression must be preserved or even enhanced. To investigate how such genes evade host shutoff, we analyzed the expression of a set of cellular transcripts in Burkitt lymphoma cells, sorted 24 hours after exposure to lytic triggers, into lytic and refractory (non-lytic) populations. We identified a subset of host transcripts consistently upregulated in lytic cells across Burkitt lymphoma lines reactivated by functionally distinct lytic stimuli, indicating that such upregulation is independent of pleiotropic lytic cycle inducing stimuli. Importantly, we found that while ZEBRA suppresses protein expression of some of these host (and select viral) genes, EBV also transcriptionally upregulates two related host genes,\n                    <jats:italic>ELAVL4<\/jats:italic>\n                    and\n                    <jats:italic>PABPC4L<\/jats:italic>\n                    . Both encode RNA-binding proteins, and we found that they differentially modulate viral transcript abundance \u2013 enhancing some while repressing others \u2013 ultimately supporting the transcriptional demands, efficient genome replication and virion release during the EBV lytic cycle. These findings highlight the virus\u2019s finely tuned regulation of both host and viral gene expression to ensure successful completion of the lytic cycle. Specifically, they suggest that EBV selectively upregulates critical host genes to counteract\/escape host shutoff and promote virus propagation.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014211","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T17:45:22Z","timestamp":1778521522000},"page":"e1014211","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Playing both sides \u2013 Epstein-Barr Virus accumulates select cellular transcripts to counter virus-mediated host shut-off in lytic cells"],"prefix":"10.1371","volume":"22","author":[{"given":"Derek","family":"Daigle","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashton","family":"Creasy-Marrazzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyn","family":"Gradoville","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayman","family":"El-Guindy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rishabh","family":"Mukherjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandeepan","family":"Das","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Budhadev","family":"Baral","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth A.","family":"Rousseau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael T.","family":"McIntosh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2946-9497","authenticated-orcid":true,"given":"Sumita","family":"Bhaduri-McIntosh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,5,11]]},"reference":[{"issue":"1","key":"ppat.1014211.ref001","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s00432-021-03824-y","article-title":"Estimating the global burden of Epstein-Barr 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Park","year":"2014","journal-title":"PLoS One"},{"issue":"7","key":"ppat.1014211.ref005","article-title":"Nascent transcriptomics reveal cellular prolytic factors upregulated upstream of the latent-to-lytic switch protein of Epstein-Barr virus","volume":"94","author":"TR Frey","year":"2020","journal-title":"J Virol"},{"issue":"10","key":"ppat.1014211.ref006","doi-asserted-by":"crossref","first-page":"114743","DOI":"10.1016\/j.celrep.2024.114743","article-title":"Epstein-Barr virus induces host shutoff extensively via BGLF5-independent mechanisms","volume":"43","author":"A Casco","year":"2024","journal-title":"Cell Rep"},{"issue":"1","key":"ppat.1014211.ref007","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/0042-6822(79)90455-0","article-title":"Induction of the Epstein-Barr virus (EBV) cycle in latently infected cells by n-butyrate","volume":"94","author":"J 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