Fig. 2.

SARS-CoV-2 recognition by nucleic acid sensors and activation of pro-inflammatory and antiviral responses. Following SARS-CoV-2 infection, viral particles are contained within endosomal compartments. Here, viral ssRNA is released and can be recognized by TLR7 and TLR8, which activate downstream signaling pathways converging to the activation of NF-kB, IRF3, and IRF7. NF-kB promotes the transcription of pro-inflammatory cytokines such as pro-IL-1β and the inflammasome component NLRP3. The inflammasome promotes the maturation of pro-IL-1β in mature IL-1β, which can be secreted. NF-kB cooperates also with IRF3 and IRF7 for the expression of type I IFNs. When the viral ssRNA is released in the cytoplasm, it is replicated by an RNA-dependent RNA polymerase which forms dsRNA intermediates. dsRNA can be recognized by cytoplasmic sensors such as RIG-I and MDA5, which converge to the activation of IRF3 and IRF7. Type I IFNs can act in an autocrine manner, activating STAT1 and STAT2 and thus promoting the expression of interferon-stimulated genes involved in anti-viral defense.