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. 2022 Jan 3;434(6):167438. doi: 10.1016/j.jmb.2021.167438

Figure 1.

Figure 1

Mechanism of innate immune activation and control of viral infection. Recognition of viral RNA by cytoplasmic RIG-I-like receptors or endosomal TLRs activates signaling cascades leading to the production of IFNs, inflammatory cytokines and chemokines. IFNs bind to their specific receptors to activate JAK-STAT signaling pathway to induce the expression of hundreds of ISGs. While many of ISGs encode proteins that regulate innate immune response, some of them directly inhibit distinct steps of viral replication. Genetic evidence of innate immunity genes affecting COVID-19 severity was revealed in a GWAS report with hits in IFNAR2, TYK2 and OAS1 (RAF, risk allele frequency in the UK Biobank) as well as in studies that discovered at least 3.5% of patients with life-threatening COVID-19 carry rare loss-of-function (LOF) genetic variants in innate immunity genes (TLR3, TLR7, IRF7, IRF3, IFNAR1 and IFNAR2). These genes impair the type I and II IFN response to SARS-COVID-2 and are marked with a red cross. See text for further interpretation.