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

Luca D. Bertzbach, Maria Laparidou, Sonja Härtle, Robert J. Etches, Bernd Kaspers, Benjamin Schusser, Benedikt B. Kaufer

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)11603-11607
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number45
DOIs
StatePublished - 6 Nov 2018

Keywords

  • B cells
  • Ig knockout chickens
  • Lymphomagenesis
  • Marek's disease virus
  • Transgenic chickens

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