Induction of DNA Damages upon Marek's Disease Virus Infection: Implication in Viral Replication and Pathogenesis
| Autor: | Sylvie Rémy, Caroline Denesvre, Luca D. Bertzbach, Yves Le Vern, Tereza Vychodil, Laëtitia Trapp-Fragnet, Djihad Bencherit, Benedikt B. Kaufer |
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| Přispěvatelé: | Trapp-Fragnet, Laëtitia, Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), Institut für Virologie, Free University of Berlin (FU), Institut National de la Recherche Agronomique (INRA)-Université de Tours |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Virologie Viral pathogenesis animal diseases viruses medicine.disease_cause Virus Replication law.invention 0302 clinical medicine réplication virale law hemic and lymphatic diseases DNA Breaks Double-Stranded pathogénèse biology Cell Cycle virus diseases Cell cycle 3. Good health Virus-Cell Interactions Santé publique et épidémiologie Cell Transformation Neoplastic Lytic cycle 030220 oncology & carcinogenesis [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology Recombinant DNA Marek's disease virus animal structures DNA damage Immunology poulet Herpesvirus oncogenesis viral replication VP22 virus Microbiology maladie de marek 03 medical and health sciences Viral Proteins herpes virus aviaire Virology medicine Marek Disease Animals Herpesvirus 2 Gallid Poultry Diseases Marek's disease biology.organism_classification Cell Transformation Viral 030104 developmental biology Viral replication Insect Science DNA Viral Leukocytes Mononuclear [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie Virus Activation Carcinogenesis Chickens |
| Zdroj: | Journal of Virology 24 (91), 1-36. (2017) Journal of Virology Journal of Virology, American Society for Microbiology, 2017, 91 (24), 16 p. ⟨10.1128/JVI.01658-17⟩ |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/JVI.01658-17⟩ |
| Popis: | Marek's disease virus (MDV) is a highly contagious alphaherpesvirus that infects chickens and causes a deadly neoplastic disease. We previously demonstrated that MDV infection arrests cells in S phase and that the tegument protein VP22 plays a major role in this process. In addition, expression of VP22 induces double-strand breaks (DSBs) in the cellular DNA, suggesting that DNA damage and the associated cellular response might be favorable for the MDV life cycle. Here, we addressed the role of DNA damage in MDV replication and pathogenesis. We demonstrated that MDV induces DSBs during lytic infection in vitro and in the peripheral blood mononuclear cells of infected animals. Intriguingly, we did not observe DNA damage in latently infected MDV-induced lymphoblastoid cells, while MDV reactivation resulted in the onset of DNA lesions, suggesting that DNA damage and/or the resulting DNA damage response might be required for efficient MDV replication and reactivation. In addition, reactivation was significantly enhanced by the induction of DNA damage using a number of chemicals. Finally, we used recombinant viruses to show that VP22 is required for the induction of DNA damage in vivo and that this likely contributes to viral oncogenesis. IMPORTANCE Marek's disease virus is an oncogenic alphaherpesvirus that causes fatal T-cell lymphomas in chickens. MDV causes substantial losses in the poultry industry and is also used in small-animal models for virus-induced tumor formation. DNA damage not only is implicated in tumor development but also aids in the life cycle of several viruses; however, its role in MDV replication, latency, and reactivation remains elusive. Here, we demonstrate that MDV induces DNA lesions during lytic replication in vitro and in vivo . DNA damage was not observed in latently infected cells; however, it was reinitiated during reactivation. Reactivation was significantly enhanced by the induction of DNA damage. Recombinant viruses that lacked the ability to induce DNA damage were defective in their ability to induce tumors, suggesting that DNA damage might also contribute to cellular transformation processes leading to MDV lymphomagenesis. |
| Databáze: | OpenAIRE |
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