title: The intrinsic antiviral defense to incoming HSV-1 genomes includes specific DNA repair proteins and is counteracted by the viral protein ICP0.
abstract: Cellular restriction factors responding to herpesvirus infection include the ND10 components PML, Sp100 and hDaxx. During the initial stages of HSV-1 infection, novel sub-nuclear structures containing these ND10 proteins form in association with incoming viral genomes. We report that several cellular DNA damage response proteins also relocate to sites associated with incoming viral genomes where they contribute to the cellular front line defense. We show that recruitment of DNA repair proteins to these sites is independent of ND10 components, and instead is coordinated by the cellular ubiquitin ligases RNF8 and RNF168. The viral protein ICP0 targets RNF8 and RNF168 for degradation, thereby preventing the deposition of repressive ubiquitin marks and counteracting this repair protein recruitment. This study highlights important parallels between recognition of cellular DNA damage and recognition of viral genomes, and adds RNF8 and RNF168 to the list of factors contributing to the intrinsic antiviral defense against herpesvirus infection.
authors.affiliation: Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, California, United States of America.
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Lilley
authors.forename: Mira S
authors.initials: MS
authors.lastname: Chaurushiya
authors.forename: Chris
authors.initials: C
authors.lastname: Boutell
authors.forename: Roger D
authors.initials: RD
authors.lastname: Everett
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Weitzman
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology; D016679:Genome, Viral / Q000276:immunology*; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000276:immunology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D057131:Immune Evasion / Q000235:genetics / Q000502:physiology; D007113:Immunity, Innate / Q000235:genetics* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D011499:Protein Processing, Post-Translational; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014709:Vero Cells; D014780:Viruses / Q000276:immunology
chemical_list: D004268:DNA-Binding Proteins; D017874:Immediate-Early Proteins; C486521:RNF8 protein, human; C535210:RNF168 protein, human; D044767:Ubiquitin-Protein Ligases; C051804:Vmw110 protein, Human herpesvirus 1; D045643:DNA Repair Enzymes