PDGFRα+ fibroblasts are a major site of cytomegalovirus replication in vivo and genome maintenance during latency

Abstract

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