Publication Database

Induction of DNA damages upon Marek's disease virus infection:
implication in viral replication and pathogenesis (2017)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Bencherit, Djihad

Remy, Sylvie

Le Vern, Yves

Vychodil, Tereza (WE 5)

Bertzbach, Luca D (WE 5)

Kaufer, Benedikt B (WE 5)

Denesvre, Caroline

Trapp-Fragnet, Laëtitia

Quelle

Journal of virology : publ. by the American Society for Microbiology

Bandzählung: 91

Heftzählung: 24

Seiten: Artikelnr. e01658-17

ISSN: 1098-5514

Sprache

Englisch

Verweise

DOI: 10.1128/JVI.01658-17

Kontakt

Institut für Virologie

Robert-von-Ostertag-Str. 7-13
14163 Berlin
+49 30 838 51833
virologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

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.