Marek's Disease Virus Infection of Natural Killer Cells
Marek's Disease Virus Infection of Natural Killer Cells
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DOI：
10.3390/microorganisms7120588
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发表时间：
2019-12-01
期刊：
影响因子：
4.5
通讯作者：
Jansen, Christine A.
中科院分区：
文献类型：
--
作者：
Bertzbach, Luca D.;van Haarlem, Daphne A.;Jansen, Christine A.
自然杀伤（NK）细胞是先天免疫反应的关键参与者。它们杀死病毒感染的细胞，对诱导适应性免疫反应至关重要。马立克氏病病毒（MDV）是一种高度传染性的α疱疹病毒，可导致鸡的致命性T细胞淋巴瘤。宿主对MDV的抗性与NK细胞应答的差异有关;然而，NK细胞在控制MDV中的确切作用仍然未知。在这项研究中，我们评估了MDV是否可以感染NK细胞并改变其活化。令人惊讶的是，我们可以证明，原代鸡NK细胞非常有效地感染了非常毒力的RB-1B MDV和减毒活疫苗CVI 988。流式细胞术分析显示RB-1B和CVI 988均增强NK细胞脱粒并增加体外干扰素γ（IFN γ）产生。此外，我们可以证明MDV Eco Q编码的癌基因（meq）有助于使用meq敲除病毒诱导NK细胞活化。总之，我们的数据首次揭示了NK细胞可有效感染MDV，并且这种致癌α疱疹病毒在体外增强NK细胞脱粒并增加IFN γ的产生。
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 (IFN gamma) 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 IFN gamma production in vitro.