https://phaidra.vetmeduni.ac.at/o:2295 Fibroblasts are a site of murine cytomegalovirus lytic replication and Stat1-dependent latent persistence in vivo Sitnik, Katarzyna M. Katarzyna M. Sitnik 0000-0002-6965-0322 University of Veterinary Medicine Vienna / Helmholtz Centre for Infection Research Čičin-Šain, Luka Luka Čičin-Šain 0000-0003-3978-778X Helmholtz Centre for Infection Research / German Centre for Infection Research Brizić, Ilija Ilija Brizić 0000-0001-8839-7839 University of Rijeka Kim, Yeonsu Yeonsu Kim Helmholtz Centre for Infection Research Maaß, Henrike Henrike Maaß 0000-0002-4654-5423 Helmholtz Centre for Infection Research Kubsch, Tobias Tobias Kubsch Helmholtz Centre for Infection Research Rand, Ulfert Ulfert Rand 0000-0002-5946-4921 Helmholtz Centre for Infection Research Krstanović, Fran Fran Krstanović 0000-0003-2779-0359 University of Rijeka Gödecke, Natascha Natascha Gödecke 0000-0002-6578-6601 Helmholtz Centre for Infection Research Nature Portfolio text eng 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. Virus Infection; Cells; Reactivation; Establishment; Pathogenesis; Macrophage; Growth; Gamma http://creativecommons.org/licenses/by/4.0/ https://phaidra.vetmeduni.ac.at/api/object/o:2295/download 10.1038/s41467-023-38449-x https://phaidra.vetmeduni.ac.at/o:605 application/pdf Nature Communications 14(1) (2023) Nature Communications 14 1 2.29 MB 2023