Abstract
Natural killer (NK) cells are key players in the innate immune response. They kill virus-infected cells and are crucial for the induction of adaptive immune responses. Marek’s disease virus (MDV) is a highly contagious alphaherpesvirus that causes deadly T cell lymphomas in chickens. Host resistance to MDV is associated with differences in NK cell responses; however, the exact role of NK cells in the control of MDV remains unknown. In this study, we assessed if MDV can infect NK cells and alter their activation. Surprisingly, we could demonstrate that primary chicken NK cells are very efficiently infected with very virulent RB-1B MDV and the live-attenuated CVI988 vaccine. Flow cytometry analysis revealed that both RB-1B and CVI988 enhance NK cell degranulation and increase interferon gamma (IFNγ) production in vitro. In addition, we could show that the MDV Eco Q-encoded oncogene (meq) contributes to the induction of NK cell activation using meq knockout viruses. Taken together, our data revealed for the first time that NK cells are efficiently infectable with MDV and that this oncogenic alphaherpesvirus enhances NK cell degranulation and increased IFNγ production in vitro.
Highlights
Marek’s disease virus (MDV) is an alphaherpesvirus that causes deadly lymphomas in chickens with a mortality of up to 100% [1]
We identified markers that are expressed on chicken natural killer (NK) cells and developed assays to measure NK cell degranulation and killing [21]
Our study provides the first evidence that NK cells are efficiently infected, highlighting a so far unknown tropism of this highly oncogenic herpesvirus
Summary
Marek’s disease virus (MDV) is an alphaherpesvirus that causes deadly lymphomas in chickens with a mortality of up to 100% [1]. We identified markers that are expressed on chicken NK cells and developed assays to measure NK cell degranulation and killing [21] We used these tools and recombinant viruses to determine if MDV can infect NK cells and if this affects NK cell degranulation and IFNγ secretion. We demonstrate that both a very virulent strain and the CVI988 vaccine strain efficiently infect primary chicken NK cells. In these infected cultures, we observed an increased NK cell degranulation and IFNγ production. Our study provides the first evidence that NK cells are efficiently infected, highlighting a so far unknown tropism of this highly oncogenic herpesvirus
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