title: Tracking adenovirus genomes identifies morphologically distinct late DNA replication compartments.
abstract: In adenoviral virions, the genome is organized into a chromatin-like structure by viral basic core proteins. Consequently viral DNAs must be replicated, chromatinized and packed into progeny virions in infected cells. Although viral DNA replication centers can be visualized by virtue of viral and cellular factors, the spatiotemporal regulation of viral genomes during subsequent steps remains to be elucidated. In this study, we used imaging analyses to examine the fate of adenoviral genomes and to track newly replicated viral DNA as well as replication-related factors. We show de novo formation of a subnuclear domain, which we termed Virus-induced Post-Replication (ViPR) body, that emerges concomitantly with or immediately after disintegration of initial replication centers. Using a nucleoside analogue, we show that viral genomes continue being synthesized in morphologically distinct replication compartments at the periphery of ViPR bodies and are then transported inward. In addition, we identified a nucleolar protein Mybbp1a as a molecular marker for ViPR bodies, which specifically associated with viral core protein VII. In conclusion, our work demonstrates the formation of previously uncharacterized viral DNA replication compartments specific for late phases of infection that produce progeny viral genomes accumulating in ViPR bodies.
authors: Microbiologie Fondamentale et Pathogénicité, MFP CNRS UMR 5234, Université de Bordeaux, Bordeaux, France.|Department of Infection Biology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors: Tetsuro
authors: T
authors: Komatsu
authors: Microbiologie Fondamentale et Pathogénicité, MFP CNRS UMR 5234, Université de Bordeaux, Bordeaux, France.
authors: Derrick R
authors: DR
authors: Robinson
authors: Department of Infection Biology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors: Miharu
authors: M
authors: Hisaoka
authors: Department of Infection Biology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors: Shuhei
authors: S
authors: Ueshima
authors: Department of Infection Biology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors: Mitsuru
authors: M
authors: Okuwaki
authors: Department of Infection Biology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors: Kyosuke
authors: K
authors: Nagata
authors: Microbiologie Fondamentale et Pathogénicité, MFP CNRS UMR 5234, Université de Bordeaux, Bordeaux, France. harald.wodrich@u-bordeaux.fr.
authors: Harald
authors: H
authors: Wodrich
mesh_terms: D000256:Adenoviridae / Q000235:genetics* / Q000472:pathogenicity; D015415:Biomarkers / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000821:virology; D004261:DNA Replication / Q000235:genetics*; D004279:DNA, Viral / Q000235:genetics; D004268:DNA-Binding Proteins; D016679:Genome, Viral; D006801:Humans; D008856:Microscopy, Fluorescence; D009687:Nuclear Proteins / Q000378:metabolism; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism; D021381:Protein Transport; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D014779:Virus Replication
chemical_list: D015415:Biomarkers; D004279:DNA, Viral; D004268:DNA-Binding Proteins; C491719:MYBBP1A protein, human; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D016601:RNA-Binding Proteins; D014157:Transcription Factors
keywords: 
  EdU labeling; 
  ViPR body; Mybbp1a; adenovirus; click chemistry; nucleous; subnuclear structure