Publikationsdatenbank

Unraveling the role of B cells in the pathogenesis of an oncogenic avian herpesvirus (2018)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Bertzbach, Luca D (WE 5)

Laparidou, Maria

Härtle, Sonja

Etches, Robert J

Kaspers, Bernd

Schusser, Benjamin

Kaufer, Benedikt B (WE 5)

Quelle

Proceedings of the National Academy of Sciences of the United States of America

Bandzählung: 115

Heftzählung: 45

Seiten: 11603 – 11607

ISSN: 1091-6490

Sprache

Englisch

Verweise

DOI: 10.1073/pnas.1813964115

Pubmed: 30337483

Kontakt

Institut für Virologie

Robert-von-Ostertag-Str. 7-13
14163 Berlin
+49 30 838 51833
virologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

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.