Innate immunity provides a rapid response to viral infections, independent of prior exposure to a specific virus 1•, 2•. Innate immunity generally encompasses both intrinsic immunity, featuring constitutively expressed antiviral effectors, and induced innate immunity, which is activated by infection [3]. Host cells detect viral infections by sensing pathogen-associated molecular patterns (PAMPs) through host pattern recognition receptors (PRRs) [1]. In jawed vertebrates, PRR activation triggers the production of interferons (IFNs), a family of cytokines that act in both autocrine and paracrine manners to induce an antiviral state in infected and neighboring cells [2]. The antiviral state is a cellular condition in which the cell is primed to defend itself against viral infections through the IFN-mediated expression of numerous genes known as interferon-stimulated genes (ISGs) 4, 5.

In recent reviews in Current Opinion in Immunology, Liu and Gack discussed the induction of, and evasion strategies from the IFN response by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)RTP [1], while Bastard et al. explored how defects in IFN production and signaling contribute to severe COVID-19 [2]. These reviews highlighted the importance of the IFN response in antiviral defense. Here, we discuss how ISGs establish an antiviral state within the cell, primarily focusing on SARS-CoV-2 infection.