1. Marek’s disease virus prolongs survival of primary chicken B-cells by inducing a senescence-like phenotype
- Author
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Caroline Denesvre, Julia Schermuly, Benedikt B. Kaufer, Sonja Härtle, Florian Pfaff, Marina Kohn, Laëtitia Trapp-Fragnet, Luca D. Bertzbach, Infectiologie et Santé Publique (UMR ISP), Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Ludwig-Maximilians-Universität München (LMU), Freie Universität Berlin, Friedrich-Loeffler-Institut (FLI), INRAE, Volkswagen Foundation Lichtenberg grant A112662, ANR-13-ANWA-0002,MADISUP,Marek's Disease Virus induced immunosuppression: From diagnosis to vaccination(2013), and Université de Tours-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
- Subjects
B Cells ,Microarrays ,medicine.medical_treatment ,animal diseases ,viruses ,Gene Expression ,Apoptosis ,Immune Receptors ,Biochemistry ,Poultry ,White Blood Cells ,Animal Cells ,immune system diseases ,hemic and lymphatic diseases ,Medicine and Health Sciences ,Gamefowl ,Bursa of Fabricius ,Cell Cycle and Cell Division ,Biology (General) ,B Cell Receptors ,Cellular Senescence ,B-Lymphocytes ,0303 health sciences ,Immune System Proteins ,Cell Death ,030302 biochemistry & molecular biology ,Eukaryota ,Cell cycle ,3. Good health ,Phenotype ,Bioassays and Physiological Analysis ,Cytokine ,Lymphatic system ,Cell Processes ,Vertebrates ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Cellular Types ,Research Article ,Signal Transduction ,animal structures ,QH301-705.5 ,Immune Cells ,Autophagic Cell Death ,Immunology ,B-cell receptor ,Biology ,Research and Analysis Methods ,Microbiology ,Virus ,Birds ,03 medical and health sciences ,Virology ,Marek Disease ,Genetics ,medicine ,Animals ,Antibody-Producing Cells ,Molecular Biology ,030304 developmental biology ,Marek's disease ,Blood Cells ,[SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health ,Organisms ,Biology and Life Sciences ,Proteins ,Cell Biology ,RC581-607 ,biology.organism_classification ,Mardivirus ,Fowl ,Amniotes ,Parasitology ,Immunologic diseases. Allergy ,Chickens ,Zoology - 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.
- Published
- 2021