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Here, we reveal that the murine CMV (MCMV) protein m152 specifically targets the type I interferon (IFN) response by binding to stimulator of interferon genes (STING), thereby delaying its trafficking to the Golgi compartment from where STING initiates type I IFN signaling. Infection with an MCMV lacking m152 induced elevated type I IFN responses and this leads to reduced viral transcript levels both\n                    <jats:italic>in\u00a0vitro<\/jats:italic>\n                    and\n                    <jats:italic>in\u00a0vivo<\/jats:italic>\n                    . This effect is ameliorated in the absence of STING. Interestingly, while m152 inhibits STING\u2010mediated IRF signaling, it did not affect STING\u2010mediated NF\u2010\u03baB signaling. Analysis of how m152 targets STING translocation reveals that STING activates NF\u2010\u03baB signaling already from the ER prior to its trafficking to the Golgi. Strikingly, this response is important to promote early MCMV replication. Our results show that MCMV has evolved a mechanism to specifically antagonize the STING\u2010mediated antiviral IFN response, while preserving its pro\u2010viral NF\u2010\u03baB response, providing an advantage in the establishment of an infection.\n                  <\/jats:p>","DOI":"10.15252\/embj.2018100983","type":"journal-article","created":{"date-parts":[[2019,1,29]],"date-time":"2019-01-29T10:44:35Z","timestamp":1548758675000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":102,"title":["The herpesviral antagonist m152 reveals differential activation of STING\u2010dependent IRF and NF\u2010\u03baB signaling and STING's dual role during MCMV infection"],"prefix":"10.1038","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9240-3987","authenticated-orcid":false,"given":"Markus","family":"Stempel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baca","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanda","family":"Jurani\u0107 Lisni\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"Krmpoti\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josephine","family":"Hartung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9180-4060","authenticated-orcid":false,"given":"S\u00f8ren R","family":"Paludan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"F\u00fcllbrunn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9190-6497","authenticated-orcid":false,"given":"Niels AW","family":"Lemmermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5431-6527","authenticated-orcid":false,"given":"Melanie M","family":"Brinkmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,1,29]]},"reference":[{"key":"BFEMBJ2018100983_CR1","doi-asserted-by":"crossref","first-page":"5328","DOI":"10.1128\/JVI.00037-14","volume":"88","author":"T Abe","year":"2014","unstructured":"Abe T, Barber GN (2014) Cytosolic\u2010DNA\u2010mediated, STING\u2010dependent proinflammatory gene induction necessitates canonical NF\u2010kappaB activation through TBK1. 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