o:2295 Fibroblasts are a site of murine cytomegalovirus lytic replication and Stat1-dependent latent persistence in vivo en 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 1552099 10.1038/s41467-023-38449-x 2023-11-10T09:51:08.178Z 44 yes 46 Katarzyna M. Sitnik University of Veterinary Medicine Vienna / Helmholtz Centre for Infection Research 0000-0002-6965-0322 Fran Krstanović University of Rijeka person 0000-0003-2779-0359 Natascha Gödecke Helmholtz Centre for Infection Research person 0000-0002-6578-6601 Ulfert Rand Helmholtz Centre for Infection Research person 0000-0002-5946-4921 Tobias Kubsch Helmholtz Centre for Infection Research person Henrike Maaß Helmholtz Centre for Infection Research person 0000-0002-4654-5423 Yeonsu Kim Helmholtz Centre for Infection Research person Ilija Brizić University of Rijeka person 0000-0001-8839-7839 Luka Čičin-Šain Helmholtz Centre for Infection Research / German Centre for Infection Research person 0000-0003-3978-778X application/pdf 2396253 https://phaidra.vetmeduni.ac.at/o:2295 no yes 16 70 1552253 Nature Communications 13 14 1 Nature Portfolio 2023