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The process is also involved in events for establishing viral infection and replication. The first step in ubiquitination involves ubiquitin (Ub) binding with Ub-activating enzyme (E1, also termed UBE1) via a thioester linkage. Our results show that HSV-1 infection alters protein ubiquitination pattern in host cells, as evidenced by MS spectra and co-immunoprecipitation assays. HSV-1 induced ubiquitination of UBE1a isoform via an isopeptide bond with Lys604. Moreover, we show that ubiquitination of K604 in UBE1a enhances UBE1a activity; that is, the activity of ubiquitin-transfer to E2 enzyme. Subsequently, we investigated the functional role of UBE1a and ubiquitination of K604 in UBE1a. We found that UBE1-knockdown increased HSV-1 DNA replication and viral production. Furthermore, overexpression of UBE1a, but not a UBE1a K604A mutant, suppressed viral replication. Furthermore, we found that UBE1a and ubiquitination at K604 in UBE1a retarded expression of HSV-1 major capsid protein, ICP5. Our findings show that UBE1a functions as an antiviral factor that becomes activated upon ubiquitination at Lys604.<\/jats:p>","DOI":"10.1042\/bcj20200885","type":"journal-article","created":{"date-parts":[[2020,12,24]],"date-time":"2020-12-24T03:12:22Z","timestamp":1608779542000},"page":"261-279","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Herpes simplex virus 1 infection induces ubiquitination of UBE1a"],"prefix":"10.1042","volume":"478","author":[{"given":"Marina","family":"Ikeda","sequence":"first","affiliation":[{"name":"Department of Cell Biology, Kyoto Pharmaceutical University, Kyoto 607-8412, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadashi","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Kyoto Pharmaceutical University, Kyoto 607-8412, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Ito","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Signaling, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5165-0789","authenticated-orcid":false,"given":"Masahiro","family":"Fujimuro","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Kyoto Pharmaceutical University, Kyoto 607-8412, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2021,1,15]]},"reference":[{"key":"2021112218171042000_BCJ-2020-0885C1","first-page":"2501","volume-title":"Fields Virology","author":"Knipe","year":"2007","edition":"5th edn"},{"key":"2021112218171042000_BCJ-2020-0885C2","doi-asserted-by":"publisher","first-page":"1513","DOI":"10.1016\/S0140-6736(00)04638-9","article-title":"Herpes simplex virus infections","volume":"357","year":"2001","journal-title":"Lancet"},{"key":"2021112218171042000_BCJ-2020-0885C3","doi-asserted-by":"publisher","first-page":"262415","DOI":"10.1155\/2010\/262415","article-title":"Towards an understanding of the herpes simplex virus type 1 latency-reactivation cycle","volume":"2010","year":"2010","journal-title":"Interdiscip. 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