The Railmap of Type I Interferon Induction: Subcellular Network Plan and How Viruses Can Change Tracks

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.