Marek's disease virus prolongs survival of primary chicken B-cells by inducing a senescence-like phenotype

Trapp-Fragnet, Laëtitia ; Schermuly, Julia ; Kohn, Marina; Bertzbach, Luca D. ; Pfaff, Florian ; Denesvre, Caroline ; Kaufer, Benedikt B. und Härtle, Sonja (2021): Marek's disease virus prolongs survival of primary chicken B-cells by inducing a senescence-like phenotype.
In: PLOS Pathogens 17(10), e1010006

Abstract

Marek’s disease virus (MDV) is an alphaherpesvirus that causes immunosuppression and deadly lymphoma in chickens. Lymphoid organs play a central role in MDV infection in animals. B-cells in the bursa of Fabricius facilitate high levels of MDV replication and contribute to dissemination at early stages of infection. Several studies investigated host responses in bursal tissue of MDV-infected chickens; however, the cellular responses specifically in bursal B-cells has never been investigated. We took advantage of our recently established in vitro infection system to decipher the cellular responses of bursal B-cells to infection with a very virulent MDV strain. Here, we demonstrate that MDV infection extends the survival of bursal B-cells in culture. Microarray analyses revealed that most cytokine/cytokine-receptor-, cell cycle- and apoptosis-associated genes are significantly down-regulated in these cells. Further functional assays validated these strong effects of MDV infections on cell cycle progression and thus, B-cell proliferation. In addition, we confirmed that MDV infections protect B-cells from apoptosis and trigger an accumulation of the autophagy marker Lc3-II. Taken together, our data indicate that MDV-infected bursal B-cells show hallmarks of a senescence-like phenotype, leading to a prolonged B-cell survival. This study provides an in-depth analysis of bursal B-cell responses to MDV infection and important insights into how the virus extends the survival of these cells.

Author summary: Upon MDV entry via the respiratory tract, B-cells are among the first cells to be infected in the lung and allow an efficient amplification of the virus. B-cells ensure the transmission of the virus to activated T-cells in which it replicates and ultimately transforms CD4-positive T-cells. Although playing a pivotal role in the MDV life cycle, the response of B-cells to MDV is currently not fully understood. Here, by using an in vitro infection model of primary bursal B-cells, we show that MDV infection leads to a prolonged B-cell survival resulting from decreased cell proliferation, protection from apoptosis and activation of autophagy. Our study provides new insights into the B-cell response to MDV infection, demonstrating that MDV triggers a senescence-like phenotype in B-cells that could potentiate their role in MDV pathogenesis.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Tiermedizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1553-7366
• Sprache: Englisch