Identification and characterization of interferon-gamma-stimulated effector proteins and interferon-gamma-repressed dependency factors effecting cytomegalovirus replication

干扰素-γ刺激的效应蛋白和干扰素-γ抑制影响巨细胞病毒复制的依赖性因子的鉴定和表征

• 批准号: 426496866
• 负责人: Professor Dr. Mirko Trilling
• 金额: --
• 依托单位: Institut für Virologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/426496866?language=en
• 关键词: Identification; characterization; interferon; gamma; stimulated

Viruses are obligate intracellular pathogens, which cause various diseases. One immediate immune response necessary to survive most viral infections is the induction of interferons (IFNs). IFNs are cytokines, which confer strong antiviral activity by changing the transcriptional program of target cells. Based on their molecular homology, receptor usage, and transcription factor activation profile, IFNs are subdivided into type I IFNs (e.g. IFN alpha/beta), type II IFN (IFN gamma) and type III IFNs (IFNλ). According to an oversimplified model, type I and III IFNs elicit direct cell-intrinsic antiviral activity, whereas IFN gamma mainly acts by enhancing adaptive immune responses. Contrasting this dichotomy, we and others observed pronounced direct antiviral activity of IFNγ against several DNA viruses. This raises the question which IFN gamma-regulated changes of the host proteome execute the antiviral activity. Using transcriptomics and proteomics, we have determined IFN gamma-specific changes. In addition to the characterization of genes preferentially induced by IFN gamma, we identified a novel class of IFN-repressed genes (IRepGs). In the proposed project, we aim to identify and characterize the IFN gamma-stimulated genes (ISG gamma) as well as the IFN gamma-dependent gene repression events, which confer the antiviral activity against cytomegaloviruses.

病毒是专性细胞内病原体，引起各种疾病。大多数病毒感染存活所必需的一种直接免疫应答是干扰素（IFN）的诱导。IFN是细胞因子，其通过改变靶细胞的转录程序来赋予强的抗病毒活性。基于它们的分子同源性、受体使用和转录因子活化谱，IFN被细分为I型IFN（例如IFN α/β）、II型IFN（IFN γ）和III型IFN（IFNλ）。根据一个过于简化的模型，I型和III型IFN引起直接的细胞内在抗病毒活性，而IFN γ主要通过增强适应性免疫应答起作用。与此相反，我们和其他人观察到IFNγ对几种DNA病毒具有明显的直接抗病毒活性。这就提出了一个问题，即IFN γ调节的宿主蛋白质组的变化执行抗病毒活性。使用转录组学和蛋白质组学，我们已经确定了IFN γ特异性的变化。除了IFN γ优先诱导的基因的表征，我们确定了一类新的IFN抑制基因（IRepGs）。在拟议的项目中，我们的目标是确定和表征IFN γ刺激的基因（ISG γ）以及IFN γ依赖的基因阻遏事件，赋予抗巨细胞病毒的抗病毒活性。