1. Cell Cycle Modulation by Marek’s Disease Virus: The Tegument Protein VP22 Triggers S-Phase Arrest and DNA Damage in Proliferating Cells
- Author
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Laëtitia Trapp-Fragnet, Gladys Mirey, Caroline Denesvre, Danièle Chabanne-Vautherot, Jean-François Vautherot, Sylvie Rémy, Elisa Boutet-Robinet, Yves Le Vern, Djihad Bencherit, Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), Contaminants & Stress Cellulaire (ToxAlim-COMICS), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Génotoxicité & Signalisation (ToxAlim-GS), European Society for Veterinary Virology (ESVV)., Trapp-Fragnet, Laëtitia, Ligue contre le Cancer du Grand-Ouest, Indre et Loire, Vendee, European Society for Virology., Institut National de la Recherche Agronomique (INRA)-Université de Tours, Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées
- Subjects
Cell cycle checkpoint ,Mardivirus ,viruses ,lcsh:Medicine ,medicine.disease_cause ,Biochemistry ,Poultry ,S Phase ,Histones ,Tegument Proteins ,Molecular Cell Biology ,Basic Cancer Research ,Medicine and Health Sciences ,DNA Breaks, Double-Stranded ,Cell Cycle and Cell Division ,lcsh:Science ,ComputingMilieux_MISCELLANEOUS ,Multidisciplinary ,Cancer Risk Factors ,Microbiology and Parasitology ,Agriculture ,Cell cycle ,Microbiologie et Parasitologie ,3. Good health ,Cell biology ,Protein Transport ,[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology ,Veterinary Diseases ,Oncology ,Cell Processes ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Viruses ,virus maladie de marek ,Cellular Structures and Organelles ,Research Article ,Subcellular Fractions ,[SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT] ,Livestock ,Viral and Bacterial Causes of Cancer ,DNA repair ,Biology ,Viral Structure ,Microbiology ,Cell Line ,Viral Proteins ,Virology ,DNA-binding proteins ,medicine ,Marek Disease ,Animals ,Cell Proliferation ,Cell Nucleus ,Marek's disease ,Biology and life sciences ,Cell growth ,lcsh:R ,Host Cells ,Organisms ,protéine de tégument ,Proteins ,DNA ,Cell Biology ,Cell Cycle Checkpoints ,Veterinary Virology ,biology.organism_classification ,Epstein–Barr virus ,cycle cellulaire ,Viral Replication ,Viral replication ,Viruses and Cancer ,lcsh:Q ,Veterinary Science ,Carcinogenesis ,DNA viruses ,Chickens ,Viral Transmission and Infection ,DNA Damage - Abstract
International audience; Marek's disease is one of the most common viral diseases of poultry affecting chicken flocks worldwide. The disease is caused by an alphaherpesvirus, the Marek's disease virus (MDV), and is characterized by the rapid onset of multifocal aggressive T-cell lymphoma in the chicken host. Although several viral oncogenes have been identified, the detailed mechanisms underlying MDV-induced lymphomagenesis are still poorly understood. Many viruses modulate cell cycle progression to enhance their replication and persistence in the host cell, in the case of some oncogenic viruses ultimately leading to cellular transformation and oncogenesis. In the present study, we found that MDV, like other viruses, is able to subvert the cell cycle progression by triggering the proliferation of low proliferating chicken cells and a subsequent delay of the cell cycle progression into S-phase. We further identified the tegument protein VP22 (pUL49) as a major MDV-encoded cell cycle regulator, as its vector-driven overexpression in cells lead to a dramatic cell cycle arrest in S-phase. This striking functional feature of VP22 appears to depend on its ability to associate with histones in the nucleus. Finally, we established that VP22 expression triggers the induction of massive and severe DNA damages in cells, which might cause the observed intra S-phase arrest. Taken together, our results provide the first evidence for a hitherto unknown function of the VP22 tegument protein in herpesviral reprogramming of the cell cycle of the host cell and its potential implication in the generation of DNA damages.
- Published
- 2014