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.
Highlights
Marek’s disease is a highly contagious disease that affects galliformes
This study provides an in-depth analysis of bursal B-cell responses to Marek’s disease virus (MDV) infection and important insights into how the virus extends the survival of these cells
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
Summary
Marek’s disease is associated with a rapid onset of T-cell lymphoma within 3 to 4 weeks post-infection, immunosuppression, and neurological disorders [1,2,3]. The causative disease agent is the Gallid alphaherpesvirus 2 (GaHV-2) that is widely known as Marek’s disease virus (MDV). The infection in the lungs of chickens remains poorly understood, it is presumed that the virus infects B-cells and antigen-presenting cells (macrophages and/or dendritic cells) that transfer the virus to primary lymphoid organs (bursa of Fabricius, spleen and thymus) [5,6,7,8]. MDV can transform latently infected CD4+ T-cells, resulting in T-cell lymphomas that are observed as early as three to four weeks post infection [6,7]. Virus reactivation from latently infected cells can occur at a later stage of infection and is accompanied by a second viremia and continuous shedding of infectious virus from the feather follicle epithelium [7]
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