Atrophy of primary lymphoid organs induced by Marek's disease virus during early infection is associated with increased apoptosis, inhibition of cell proliferation and a severe B-lymphopenia

Marek's disease is a multi-faceted highly contagious disease affecting chickens caused by the Marek's disease alphaherpesvirus (MDV). MDV early infection induces a transient immunosuppression, which is associated with thymus and bursa of Fabricius atrophy. Little is known about the cellular processes involved in primary lymphoid organ atrophy. Here, by in situ TUNEL assay, we demonstrate that MDV infection results in a high level of apoptosis in the thymus and bursa of Fabricius, which is concomitant to the MDV lytic cycle. Interestingly, we observed that in the thymus most of the MDV infected cells at 6 days post-infection (dpi) were apoptotic, whereas in the bursa of Fabricius most of the apoptotic cells were uninfected suggesting that MDV triggers apoptosis by two different modes in these two primary lymphoid organs. In addition, a high decrease of cell proliferation was observed from 6 to 14 dpi in the bursa of Fabricius follicles, and not in the thymus. Finally, with an adapted absolute blood lymphocyte count, we demonstrate a major B-lymphopenia during the two 1st weeks of infection, and propose this method as a potent non-invasive tool to diagnose MDV bursa of Fabricius infection and atrophy. Our results demonstrate that the thymus and bursa of Fabricius atrophies are related to different cell mechanisms, with different temporalities, that affect infected and uninfected cells

Atrophy of primary lymphoid organs induced by Marek's disease virus infection is associated with cell death and also inhibition of cell proliferation

National audienc

Study of mechanisms leading to atrophy of primary lymphoid organs during early infection by Marek's disease virus in hen

L’infection par le virus de la maladie de Marek (MDV) induit chez les poussins une immunosuppression précoce et transitoire associée à une atrophie du thymus (TA) et de la bourse de Fabricius (BA). L’objectif de ce travail était de mieux comprendre les mécanismes cellulaires responsables de cette atrophie. La 1ère étape de mon travail a été d'établir un modèle d'infection in vivo menant à une BA et TA suffisante et reproductible. Une fois établi, ce modèle nous a permis d’étudier l’effet du MDV au sein de ces organes à 6, 10 et 14 jours post-infection. Les résultats indiquent que l'apoptose et l'inhibition de prolifération peuvent contribuer à la BA, tandis que seule l'augmentation de l'apoptose conduit à la TA. La numération des lymphocytes sanguins, a mis en évidence une diminution des lymphocytes B durant les 2 premières semaines post-infection concomitamment à la BA. Cette technique semble donc un outil prometteur non invasif pour diagnostiquer la BA induite par le MDV. Une différence de sensibilité à la TA et BA induite par le MDV a été mise en évidence dans deux lignées de poule White Leghorn d’haplotype B différents, toutes deux très sensibles au développement des tumeurs.Marek's disease virus (MDV) infection induces early and transient immunosuppression associated with atrophy of the thymus (TA) and the bursa of Fabricius (BA) in chicks. The aim of this work was to better understand the cellular mechanisms responsible for this atrophy. The first step in my work was to establish an in vivo infection model leading to a sufficient and reproducible BA and TA. Once established, this model allowed us to study the effect of MDV in these organs at 6, 10 and 14 days post-infection. The results indicate that apoptosis and inhibition of proliferation can contribute to BA, whereas only the increase in apoptosis leads to TA. The lymphocyte blood count showed a decrease in B-lymphocytes during the first 2 weeks of infection that seems related to BA. This technique therefore seems a promising non-invasive tool to diagnose BA at early times of MDV infection. A difference in sensitivity to MDV-induced TA and BA was found in two lines White Leghorn of different B haplotype, both of which very sensitive to tumor development

Role of lymphocytes death in Marek Disease Virus-induced immunosuppression

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Identification of genes modulating the innate immune response of mammary epithelial cells to <em>Escherichia col</em>i P4

International audienc

Incorporation of the influenza A virus NA segment into virions does not require cognate non-coding sequences.

International audienceFor each influenza virus genome segment, the coding sequence is flanked by non-coding (NC) regions comprising shared, conserved sequences and specific, non-conserved sequences. The latter and adjacent parts of the coding sequence are involved in genome packaging, but the precise role of the non-conserved NC sequences is still unclear. The aim of this study is to better understand the role of the non-conserved non-coding sequences in the incorporation of the viral segments into virions. The NA-segment NC sequences were systematically replaced by those of the seven other segments. Recombinant viruses harbouring two segments with identical NC sequences were successfully rescued. Virus growth kinetics and serial passages were performed, and incorporation of the viral segments was tested by real-time RT-PCR. An initial virus growth deficiency correlated to a specific defect in NA segment incorporation. Upon serial passages, growth properties were restored. Sequencing revealed that the replacing 5'NC sequence length drove the type of mutations obtained. With sequences longer than the original, point mutations in the coding region with or without substitutions in the 3'NC region were detected. With shorter sequences, insertions were observed in the 5'NC region. Restoration of viral fitness was linked to restoration of the NA segment incorporation

Atrophy of primary lymphoid organs by MDV during early infection is associated with apoptosis and inhibition of cell proliferation

National audienc

Mécanismes cellulaires à l'origine de l'atrophie des organes lymphoïdes primaires induite par l'Herpesvirus de la maladie de Marek durant l'infection précoce chez le poussin

National audienc

Mécanismes cellulaires à l'origine de l'atrophie des organes lymphoïdes primaires induite par l'Herpesvirus de la maladie de Marek durant l'infection précoce chez le poussin

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