Virus Infection; Cells; Reactivation; Establishment; Pathogenesis; Macrophage; Growth; Gamma To date, no herpesvirus has been shown to latently persist in fibroblastic cells. Here, we show that murine cytomegalovirus, a β-herpesvirus, persists for the long term and across organs in PDGFRα-positive fibroblastic cells, with similar or higher genome loads than in the previously known sites of murine cytomegalovirus latency. Whereas murine cytomegalovirus gene transcription in PDGFRα-positive fibroblastic cells is almost completely silenced at 5 months post-infection, these cells give rise to reactivated virus ex vivo, arguing that they support latent murine cytomegalovirus infection. Notably, PDGFRα-positive fibroblastic cells also support productive virus replication during primary murine cytomegalovirus infection. Mechanistically, Stat1-deficiency promotes lytic infection but abolishes latent persistence of murine cytomegalovirus in PDGFRα-positive fibroblastic cells in vivo. In sum, fibroblastic cells have a dual role as a site of lytic murine cytomegalovirus replication and a reservoir of latent murine cytomegalovirus in vivo and STAT1 is required for murine cytomegalovirus latent persistence in vivo. CC BY 4.0 International http://creativecommons.org/licenses/by/4.0/ 2023 Nature Portfolio eng Sitnik, Katarzyna M. (University of Veterinary Medicine Vienna / Helmholtz Centre for Infection Research) Čičin-Šain, Luka (Helmholtz Centre for Infection Research / German Centre for Infection Research) Brizić, Ilija (University of Rijeka) Kim, Yeonsu (Helmholtz Centre for Infection Research) Maaß, Henrike (Helmholtz Centre for Infection Research) Kubsch, Tobias (Helmholtz Centre for Infection Research) Rand, Ulfert (Helmholtz Centre for Infection Research) Krstanović, Fran (University of Rijeka) Gödecke, Natascha (Helmholtz Centre for Infection Research) Fibroblasts are a site of murine cytomegalovirus lytic replication and Stat1-dependent latent persistence in vivo Nature Communications 14(1) (2023) doi:10.1038/s41467-023-38449-x https://phaidra.vetmeduni.ac.at/o:2295 application/pdf article