Sitnik, Katarzyna M. (University of Veterinary Medicine Vienna / Helmholtz Centre for Infection Research) Katarzyna M. Sitnik Čičin-Šain, Luka (Helmholtz Centre for Infection Research / German Centre for Infection Research) Luka Čičin-Šain Brizić, Ilija (University of Rijeka) Ilija Brizić Kim, Yeonsu (Helmholtz Centre for Infection Research) Yeonsu Kim Maaß, Henrike (Helmholtz Centre for Infection Research) Henrike Maaß Kubsch, Tobias (Helmholtz Centre for Infection Research) Tobias Kubsch Rand, Ulfert (Helmholtz Centre for Infection Research) Ulfert Rand Krstanović, Fran (University of Rijeka) Fran Krstanović Gödecke, Natascha (Helmholtz Centre for Infection Research) Natascha Gödecke Nature Portfolio 2023 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. PDFDocument en 2023-11-10T09:51:08.178Z Virus Infection; Cells; Reactivation; Establishment; Pathogenesis; Macrophage; Growth; Gamma 2396253 b application/pdf CC BY 4.0 International