The review by Randall and Goodbourn provides an in-depth analysis of the interferon (IFN) system and its interaction with viruses. IFNs are a group of cytokines that play a crucial role in antiviral responses, capable of controlling most virus infections without adaptive immunity. The review covers the induction of IFNs by viruses, the mechanisms of action of IFN-induced proteins, and how viruses circumvent these responses. It highlights the importance of different signaling pathways, such as those involving TLRs (Toll-like receptors), RNA helicases (RIG-I and mda-5), and cytoplasmic DNA sensors, in recognizing viral components and initiating the IFN response. The review also discusses the role of transcription factors like IRF-3, NF-κB, and c-jun/ATF-2 in IFN induction and the complex signaling pathways involved. Additionally, it explores the implications of IFN evasion by viruses, including the modulation of viral life cycles and the potential consequences for both the virus and host. Finally, the review touches on the practical applications of this knowledge, such as vaccine design, antiviral drug development, and the use of IFN-sensitive oncolytic viruses in cancer treatment.The review by Randall and Goodbourn provides an in-depth analysis of the interferon (IFN) system and its interaction with viruses. IFNs are a group of cytokines that play a crucial role in antiviral responses, capable of controlling most virus infections without adaptive immunity. The review covers the induction of IFNs by viruses, the mechanisms of action of IFN-induced proteins, and how viruses circumvent these responses. It highlights the importance of different signaling pathways, such as those involving TLRs (Toll-like receptors), RNA helicases (RIG-I and mda-5), and cytoplasmic DNA sensors, in recognizing viral components and initiating the IFN response. The review also discusses the role of transcription factors like IRF-3, NF-κB, and c-jun/ATF-2 in IFN induction and the complex signaling pathways involved. Additionally, it explores the implications of IFN evasion by viruses, including the modulation of viral life cycles and the potential consequences for both the virus and host. Finally, the review touches on the practical applications of this knowledge, such as vaccine design, antiviral drug development, and the use of IFN-sensitive oncolytic viruses in cancer treatment.