Unraveling the role of B cells in the pathogenesis of an oncogenic avian herpesvirus

Marek’s disease virus (MDV) is a highly oncogenic alphaherpesvirus that causes immunosuppression, paralysis, and deadly lymphomas in chickens. In infected animals, B cells are efficiently infected and are thought to amplify the virus and transfer it to T cells. MDV subsequently establishes latency i...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2018-11, Vol.115 (45), p.11603-11607
Main Authors: Bertzbach, Luca D., Laparidou, Maria, Härtle, Sonja, Etches, Robert J., Kaspers, Bernd, Schusser, Benjamin, Kaufer, Benedikt B.
Format: Article
Language:English
Subjects:
Animal diseases
Animals
Animals, Genetically Modified
Animals, Newborn
B-Lymphocytes - immunology
Biological Sciences
Bursa of Fabricius
Bursa of Fabricius - immunology
Bursa of Fabricius - virology
CD4 antigen
CD4-Positive T-Lymphocytes - immunology
CD4-Positive T-Lymphocytes - virology
CD8 antigen
CD8-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - virology
Chick Embryo
Chickens
DNA, Viral - genetics
DNA, Viral - immunology
Genetic transformation
Genetics
Genome, Viral
Herpes viruses
Herpesvirus 2, Gallid - genetics
Herpesvirus 2, Gallid - immunology
Herpesvirus 2, Gallid - pathogenicity
Immunoglobulin Heavy Chains - genetics
Immunoglobulins
Immunosuppression
J gene
Latency
Lymphocyte Count
Lymphocytes
Lymphocytes B
Lymphocytes T
Lymphoma
Lymphoma - genetics
Lymphoma - immunology
Lymphoma - pathology
Lymphoma - virology
Marek Disease - genetics
Marek Disease - immunology
Marek Disease - pathology
Marek Disease - virology
Marek's disease
Oncogenic Viruses - genetics
Oncogenic Viruses - immunology
Oncogenic Viruses - pathogenicity
Organs
Paralysis
Pathogenesis
Poultry
Spleen
Spleen - immunology
Spleen - virology
Thymus
Thymus Gland - immunology
Thymus Gland - virology
Viral Load
Virulence
Virus Replication
Viruses
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Description
Summary:Marek’s disease virus (MDV) is a highly oncogenic alphaherpesvirus that causes immunosuppression, paralysis, and deadly lymphomas in chickens. In infected animals, B cells are efficiently infected and are thought to amplify the virus and transfer it to T cells. MDV subsequently establishes latency in T cells and transforms CD4⁺ T cells, resulting in fatal lymphomas. Despite many years of research, the exact role of the different B and T cell subsets in MDV pathogenesis remains poorly understood, mostly due to the lack of reverse genetics in chickens. Recently, Ig heavy chain J gene segment knockout (JH-KO) chickens lacking mature and peripheral B cells have been generated. To determine the role of these B cells in MDV pathogenesis, we infected JH-KO chickens with the very virulent MDV RB1B strain. Surprisingly, viral load in the blood of infected animals was not altered in the absence of B cells. More importantly, disease and tumor incidence in JH-KO chickens was comparable to wild-type animals, suggesting that both mature and peripheral B cells are dispensable for MDV pathogenesis. Intriguingly, MDV efficiently replicated in the bursa of Fabricius in JH-KO animals, while spread of the virus to the spleen and thymus was delayed. In the absence of B cells, MDV readily infected CD4⁺ and CD8⁺ T cells, allowing efficient virus replication in the lymphoid organs and transformation of T cells. Taken together, our data change the dogma of the central role of B cells, and thereby provide important insights into MDV pathogenesis.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1813964115