IFN response regulation upon viral infections.

Abstract

Interferons are key mediators of antiviral defense. They enable infected cells and specialized immune populations to mount rapid transcriptional responses that restrict viral replication and support immune activation. Type I and type III interferons share many antiviral properties, but their effects are determined by distinct receptor distributions, signaling dynamics, and tissue localization. While both families contribute to protection against infection, this chapter focuses primarily on the regulation and function of type I interferons. The induction of interferons depends on the activation of pattern recognition receptors that detect viral nucleic acids and trigger signaling cascades involving IRF and NF-κB transcription factors. These pathways control tightly regulated transcriptional and epigenetic programs that drive interferon gene expression and the induction of interferon-stimulated genes. Balanced regulation is essential, as excessive or persistent signaling can cause immunopathology and chronic inflammation. Genetic variation in interferon pathways influences susceptibility to viral infections, and defects in interferon regulation contribute to several monogenic interferonopathies. Plasmacytoid dendritic cells are a major source of type I interferons and illustrate the complexity of cellular specialization in antiviral defense. Understanding these mechanisms is essential for the development of therapies that enhance antiviral protection or limit pathogenic inflammation in chronic infections and autoimmune disease.