title: Upstream binding factor inhibits herpes simplex virus replication.
abstract: Herpes simplex virus 1 (HSV-1) infection induces changes to the host cell nucleus including relocalization of the cellular protein Upstream Binding Factor (UBF) from the nucleolus to viral replication compartments (VRCs). Herein, we tested the hypothesis that UBF is recruited to VRCs to promote viral DNA replication. Surprisingly, infection of UBF-depleted HeLa cells with HSV-1 or HSV-2 produced higher viral titers compared to controls. Reduced expression of UBF also led to a progressive increase in the relative amount of HSV-1 DNA versus controls, and increased levels of HSV-1 ICP27 and TK mRNA and protein, regardless of whether viral DNA replication was inhibited or not. Our results suggest that UBF can inhibit gene expression from viral DNA prior to its replication. A similar but smaller effect on viral titers was observed in human foreskin fibroblasts. This is the first report of UBF having a restrictive effect on replication of a virus.
authors.affiliation: INRS-Institut Armand-Frappier, Laval, Québec, Canada.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Ouellet Lavallée
authors.affiliation: INRS-Institut Armand-Frappier, Laval, Québec, Canada. Electronic address: angela.pearson@iaf.inrs.ca.
authors.forename: Angela
authors.initials: A
authors.lastname: Pearson
mesh_terms: D002478:Cells, Cultured; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D004847:Epithelial Cells / Q000821:virology; D005347:Fibroblasts / Q000821:virology; D015967:Gene Expression Regulation, Viral; D018259:Herpesvirus 1, Human / Q000502:physiology*; D018258:Herpesvirus 2, Human / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D035463:Pol1 Transcription Initiation Complex Proteins / Q000378:metabolism*; D019562:Viral Load; D014764:Viral Proteins / Q000032:analysis; D014779:Virus Replication
chemical_list: D004279:DNA, Viral; D035463:Pol1 Transcription Initiation Complex Proteins; D014764:Viral Proteins; C063844:transcription factor UBF
keywords: Herpes simplex virus; Intrinsic antiviral response; Upstream Binding Factor; Viral DNA replication; Viral transcription