title: Promoter-Targeted Histone Acetylation of Chromatinized Parvoviral Genome Is Essential for the Progress of Infection.
abstract: The association of host histones with parvoviral DNA is poorly understood. We analyzed the chromatinization and histone acetylation of canine parvovirus DNA during infection by confocal imaging andin situproximity ligation assay combined with chromatin immunoprecipitation and high-throughput sequencing. We found that during late infection, parvovirus replication bodies were rich in histones bearing modifications characteristic of transcriptionally active chromatin, i.e., histone H3 lysine 27 acetylation (H3K27ac). H3K27ac, in particular, was located in close proximity to the viral DNA-binding protein NS1. Importantly, our results show for the first time that in the chromatinized parvoviral genome, the two viral promoters in particular were rich in H3K27ac. Histone acetyltransferase (HAT) inhibitors efficiently interfered with the expression of viral proteins and infection progress. Altogether, our data suggest that the acetylation of histones on parvoviral DNA is essential for viral gene expression and the completion of the viral life cycle.
  
  
  OBJECTIVE
  Viral DNA introduced into cell nuclei is exposed to cellular responses to foreign DNA, including chromatinization and epigenetic silencing, both of which determine the outcome of infection. How the incoming parvovirus resists cellular epigenetic downregulation of its genes is not understood. Here, the critical role of epigenetic modifications in the regulation of parvovirus infection was demonstrated. We showed for the first time that a successful parvovirus infection is characterized by the deposition of nucleosomes with active histone acetylation on the viral promoter areas. The results provide new insights into the regulation of parvoviral gene expression, which is an important aspect of the development of parvovirus-based virotherapy.
authors: Department of Biological and Environmental Science and Nanoscience Center, University of Jyvaskyla, Jyvaskyla, Finland.
authors: Elina
authors: E
authors: Mäntylä
authors: Department of Biological and Environmental Science and Nanoscience Center, University of Jyvaskyla, Jyvaskyla, Finland.
authors: Kari
authors: K
authors: Salokas
authors: Tampere Center for Child Health Research, University of Tampere, Tampere, Finland.
authors: Mikko
authors: M
authors: Oittinen
authors: Department of Physics and Nanoscience Center, University of Jyvaskyla, Jyvaskyla, Finland.
authors: Vesa
authors: V
authors: Aho
authors: Department of Biological and Environmental Science and Nanoscience Center, University of Jyvaskyla, Jyvaskyla, Finland.
authors: Pekka
authors: P
authors: Mäntysaari
authors: Department of Biological and Environmental Science and Nanoscience Center, University of Jyvaskyla, Jyvaskyla, Finland.
authors: Lassi
authors: L
authors: Palmujoki
authors: Department of Biological and Environmental Science and Nanoscience Center, University of Jyvaskyla, Jyvaskyla, Finland.
authors: Olli
authors: O
authors: Kalliolinna
authors: NeuroGroup, BioMediTech, University of Tampere, Tampere, Finland.
authors: Teemu O
authors: TO
authors: Ihalainen
authors: Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
authors: Einari A
authors: EA
authors: Niskanen
authors: Department of Physics and Nanoscience Center, University of Jyvaskyla, Jyvaskyla, Finland.
authors: Jussi
authors: J
authors: Timonen
authors: Tampere Center for Child Health Research, University of Tampere, Tampere, Finland keijo.viiri@uta.fi maija.vihinen-ranta@jyu.fi.
authors: Keijo
authors: K
authors: Viiri
authors: Department of Biological and Environmental Science and Nanoscience Center, University of Jyvaskyla, Jyvaskyla, Finland keijo.viiri@uta.fi maija.vihinen-ranta@jyu.fi.
authors: Maija
authors: http://orcid.org/0000-0003-0959-1153
authors: M
authors: Vihinen-Ranta
mesh_terms: D000107:Acetylation; D000818:Animals; D002415:Cats; D002460:Cell Line; D002843:Chromatin / Q000821:virology*; D004279:DNA, Viral / Q000378:metabolism; D044127:Epigenesis, Genetic; D015967:Gene Expression Regulation, Viral; D016679:Genome, Viral; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D018613:Microscopy, Confocal; D010322:Parvoviridae Infections / Q000821:virology*; D017993:Parvovirus, Canine / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D016662:Virus Integration
chemical_list: D002843:Chromatin; D004279:DNA, Viral; D006657:Histones; D008239:Lysine