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Our understanding of the mechanisms underlying latency and reactivation remains incomplete. Here, we show the cellular transcription factor, activator protein-1 (AP-1), is a key to regulating HCMV reactivation. Our findings reveal AP-1 binding to the major immediate early enhancer\/promoter is critical for switching this locus from one that is repressed during latency to one that is highly active following reactivation. Our work provides a mechanism HCMV exploits to reactivate, highlighting AP-1 as a potential target to prevent HCMV reactivation.<\/jats:p>","DOI":"10.1073\/pnas.2009420117","type":"journal-article","created":{"date-parts":[[2020,8,11]],"date-time":"2020-08-11T17:01:04Z","timestamp":1597165264000},"page":"20860-20867","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":37,"title":["Activator protein-1 transactivation of the major immediate early locus is a determinant of cytomegalovirus reactivation from latency"],"prefix":"10.1073","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0919-2961","authenticated-orcid":false,"given":"Benjamin A.","family":"Krishna","sequence":"first","affiliation":[{"name":"Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7712-6259","authenticated-orcid":false,"given":"Amanda 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