{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T05:09:16Z","timestamp":1790053756554,"version":"4.0.1"},"reference-count":166,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["CA291437"],"award-info":[{"award-number":["CA291437"]}]},{"name":"NIH","award":["CA294800"],"award-info":[{"award-number":["CA294800"]}]},{"name":"NIH","award":["T32-CA071341"],"award-info":[{"award-number":["T32-CA071341"]}]},{"award":["CA291437"],"award-info":[{"award-number":["CA291437"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["CA294800"],"award-info":[{"award-number":["CA294800"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["T32-CA071341"],"award-info":[{"award-number":["T32-CA071341"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Epstein\u2013Barr Virus (EBV) is an oncogenic gammaherpesvirus present in &gt;95% of the adult population. EBV is responsible for nearly 2% of the global cancer burden and is a contributing factor in the development and progression of both epithelial and lymphoid malignancies. Throughout its lifecycle, EBV manipulates the DNA Damage Response (DDR). Aberrations in the DDR pathway result in genomic instability, a hallmark of cancer. In this review, we explore how EBV gene products expressed during lytic reactivation and latency promote genomic instability by creating a genotoxic environment and interacting with components of the DDR. Additionally, we describe viral genes capable of suppressing critical checkpoints which facilitate repair of damaged DNA. The ultimate failsafe in the case of catastrophic DNA damage is senescence or cell death, processes which are suppressed by EBV gene products. We also discuss how EBV appropriates DDR machinery to replicate its own genome during lytic reactivation. The manipulation of DDR proteins is essential for EBV-induced immortalization of primary B-cells infected in vivo, and viral strains engineered to lack these genes show reduced or ablated transformation efficacy, demonstrating the critical role of the DDR in EBV-induced oncogenesis.<\/jats:p>","DOI":"10.3390\/v18091035","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T08:03:47Z","timestamp":1789977827000},"page":"1035","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Modulation of DNA Damage by Epstein\u2013Barr Virus (EBV)"],"prefix":"10.3390","volume":"18","author":[{"given":"Emily","family":"DiMaulo-Milk","sequence":"first","affiliation":[{"name":"Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA"},{"name":"Genetics and Molecular Biology Curriculum, University of North Carolina, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9205-1774","authenticated-orcid":false,"given":"Blossom","family":"Damania","sequence":"additional","affiliation":[{"name":"Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA"},{"name":"Genetics and Molecular Biology Curriculum, University of North Carolina, Chapel Hill, NC 27599, USA"},{"name":"Department of Microbiology & Immunology, University of North Carolina, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1126\/science.1252786","article-title":"Epstein-Barr Virus Turns 50","volume":"343","author":"Lieberman","year":"2014","journal-title":"Science"},{"key":"ref_2","first-page":"433","article-title":"Epstein-Barr Virus","volume":"Volume 2","author":"Howley","year":"2021","journal-title":"Fields Virology: DNA Viruses"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3652","DOI":"10.1016\/j.cell.2022.08.026","article-title":"Epstein-Barr virus: Biology and clinical disease","volume":"185","author":"Damania","year":"2022","journal-title":"Cell"},{"key":"ref_4","first-page":"35","article-title":"Estimating the global burden of Epstein\u2013Barr virus-related cancers","volume":"148","author":"Wong","year":"2021","journal-title":"J. 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