Fibroblastic cells are a site of mouse cytomegalovirusin vivolytic replication and latent persistence oppositely regulated byStat1

AbstractTo date, no herpesvirus has been shown to latently persist in fibroblastic cells. Here, we demonstrate that mouse CMV (MCMV), a β-herpesvirus, persists for the long term and across organs in PDGFRα+fibroblastic cells, with similar or higher genome loads than in the previously known sites of MCMV latency. Whereas MCMV gene transcription in PDGFRα+fibroblastic cells was almost completely silenced at 5 months post-infection, these cells gave rise to reactivated virusex vivo, arguing that they supported latent MCMV infection. Notably, PDGFRα+fibroblastic cells also supported productive virus replication during primary MCMV infection. Mechanistically,Stat1-deficiency resulted in increased lytic but abolished latent infection of fibroblastic cellsin vivo. In sum, fibroblastic cells have a dual role as a site of lytic MCMV replication and a reservoir of latent MCMVin vivoandStat1is critically involved in the regulation of MCMV latency.