Abstract:
The innate immune response constitutes the cell\'s first line of defense against viruses and culminates in the expression of type I interferon (IFN) and IFN-stimulated genes, inducing an antiviral state in infected and neighboring cells. Efficient signal transduction is a key factor for strong but controlled type I IFN expression and depends on the compartmentalization of different steps of the signaling cascade and dynamic events between the involved compartments or organelles. This compartmentalization of the innate immune players not only relies on their association with membranous organelles but also includes the formation of supramolecular organizing centers (SMOCs) and effector concentration by liquid-liquid phase separation. For their successful replication, viruses need to evade innate defenses and evolve a multitude of strategies to impair type I IFN induction, one of which is the disruption of spatial immune signaling dynamics. This review focuses on the role of compartmentalization in ensuring an adequate innate immune response to viral pathogens, drawing attention to crucial translocation events occurring downstream of pattern recognition and leading to the expression of type I IFN. Furthermore, it intends to highlight concise examples of viral countermeasures interfering with this spatial organization to alleviate the innate immune response.
摘要:
先天性免疫反应构成细胞防御病毒的第一道防线,并最终导致I型干扰素(IFN)和IFN刺激基因的表达,在感染细胞和邻近细胞中诱导抗病毒状态。有效的信号转导是强大但受控的I型IFN表达的关键因素,并且取决于信号级联的不同步骤的区室化以及所涉及的区室或细胞器之间的动态事件。先天免疫参与者的这种区隔不仅依赖于它们与膜细胞器的关联,而且还包括通过液-液相分离形成超分子组织中心(SMOC)和效应子浓度。为了成功复制,病毒需要逃避先天防御,并进化出多种策略来削弱I型IFN诱导,其中之一是空间免疫信号动力学的破坏。这篇综述的重点是区室化在确保对病毒病原体的足够的先天免疫应答中的作用。提请注意发生在模式识别下游并导致I型IFN表达的关键易位事件。此外,它旨在强调病毒对策干扰这种空间组织以减轻先天免疫反应的简明例子。