Updated publication reference for PubMed record(s): 30833792. Defense against virus infections relies on rapid and massive engagement of cellular proteins with antiviral properties. Germline-encoded pattern recognition receptors (PRRs) sense the presence of pathogens and initiate a signaling cascade leading to the induction of antiviral cytokines, including type-I interferons. IFN-alpha/beta bind to the IFN receptor (IFNAR), initiating signaling that culminates in the expression of interferon-stimulated genes (ISGs). In sum, viral infection triggers the expression of several hundred proteins covering a wide range of biological activities. Among these proteins are PRRs (e.g. RIG-I, MDA5, TLRs), signaling molecules (e.g. MYD88, MAVS), transcription factors (e.g. IRFs, STATs) and proteins with direct antiviral functions (e.g. MX proteins, IFITs), as well as negative regulators of immune responses (e.g. SOCS proteins, DAPK1) that prevent overshooting of immune reactions. ISGs are thus a heterogeneous group of proteins that serve different purposes related to direct antiviral defense and immune regulation.